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  • hypertension  (46)
  • bioavailability  (44)
  • Springer  (89)
  • American Institute of Physics
  • Annual Reviews
  • National Academy of Sciences
  • 1980-1984  (89)
  • 1983  (54)
  • 1980  (35)
  • 1958
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  • Springer  (89)
  • American Institute of Physics
  • Annual Reviews
  • National Academy of Sciences
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  • 1980-1984  (89)
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  • 1
    Digitale Medien
    Digitale Medien
    Springer
    European journal of nutrition 22 (1983), S. 185-194 
    ISSN: 1436-6215
    Schlagwort(e): sugar substitutes ; D-glucose ; bioavailability ; D-glucitol (D-sorbitol) ; D-mannitol ; Palatinit® ; D-glucosyl-α(1→1)-D-mannitol ; D-glucosyl-α(1→6)-D-glucitol
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Land- und Forstwirtschaft, Gartenbau, Fischereiwirtschaft, Hauswirtschaft , Medizin
    Beschreibung / Inhaltsverzeichnis: Zusammenfassung Zur Vertiefung des Verständnisses vom Stoffwechsel des Zuckeraustauschstoffes Palatinit® wurden seine zwei Bestandteile D-Glucosyl-α(1→1)-D-mannit und D-Glucosyl-α(1→6)-D-glucit [D-Glucosyl-α(1→6)-D-sorbit] nach dem Verfahren von Karimzadegan et al. auf ihre Glucose-Bioverfügbarkeit an ketotischen Ratten untersucht. Bei Umwandlungsraten in Glucose von 6 bzw. 20 % für Mannit und Glucit (Sorbit) sowie von 39 bzw. 42% für Glucosylmannit und Glucosylglucit erhält demnach der metabolische Glucose-Pool nicht das volle Glucose-Äquivalent aus diesen Verbindungen. Von dem Anteil an präformierter Glucose in den Glucosylhexiten — theoretisches Maximum 50 % — sind nur 36 % aus Glucosylmannit bzw. 32 % aus Glucosylglucit bioverfügbar. Die im Vergleich zur Theorie verminderte Bioverfügbarkeit von Glucose aus Palatinit® wird auf partiellen mikrobiellen Abbau in unteren Darmabschnitten zurückgeführt. Die an Ratten erhaltenen Ergebnisse werden auch für alle anderen Spezies gelten, welche in Caecum und/oder Colon Kohlenhydrate vergären. Die Unterschiede zwischen D-Glucosyl-α(1→1)-D-mannit und D-Glucosyl-α(1→6)-D-glucit werden durch unterschiedliche Verzögerung der Glucoseresorption im Dünndarm, wo auch D-Glucit angreift, bedingt. Die Ermittlung der Glucose-Bioverfügbarkeit gewährt weitgehende Einblicke in das Schicksal von Kohlenhydraten einschließlich der Symbiose zwischen Säugetier und Mikroorganismen im Dickdarm. Da ein ziemlich vollständiger Überblick über die metabolischen Konsequenzen nach ihrer Zufuhr erhalten wird, sollte das Verfahren zur Messung der Bioverfügbarkeit von Glucose daher bei Abschätzungen der Lebensmittelsicherheit anderer Zuckeraustauschstoffe ebenfalls angewandt werden.
    Notizen: Summary For the sake of metabolic insight into the fate of the sugar substitute Palatinit®, its two components D-glucosyl-α(1→1)-D-mannitol and D-glucosyl-α(1→6)-D-glucitol [D-glucosyl-α-(1→6)-D-sorbitol] were assayed for glucose bioavailability by the procedure of Karimzadegan et al. using ketotic rats. With conversion rates into glucose of 6 and 20 %, respectively, for free mannitol and glucitol (sorbitol), 39 % for glucosylmannitol and 42 % for glucosylglucitol, the metabolic glucose pool of the rat does not receive the full carbohydrate complement of these compounds. The preformed glucose moiety of the glucosylhexitols is bioavailable by 36 and 32 %, respectively, from glucosylmannitol and glucosylglucitol, with 50 % as theoretical maximum. Less than theoretical bioavailability of glucose from Palatinit® is ascribed to microbial attack in the hindgut. The data on rats are held valid also for other species demonstrating carbohydrate fermentation in the caecum and/or colon. Differences between D-glucosyl-α(1→1)-D-mannitol and D-glucosyl-α(1→6)-D-glucitol are caused by a differential delay of glucose absorption in the small intestine, also exerted by D-glucitol. The deep metabolic insight offered by the glucose bioavailability assay into the fate of carbohydrates includes the mammal-microbial symbiosis in the large bowel. Since a rather complete survey of the metabolic consequences after their intake can be obtained, the assay system should be generally applied in assessments of food safety also of other sugar substitutes.
    Materialart: Digitale Medien
    Standort Signatur Erwartet Verfügbarkeit
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  • 2
    Digitale Medien
    Digitale Medien
    Springer
    European journal of clinical pharmacology 17 (1980), S. 111-116 
    ISSN: 1432-1041
    Schlagwort(e): zimelidine ; norzimelidine ; antidepressants ; pharmacokinetics ; bioavailability
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary The systemic availability of a new antidepressant, zimelidine, and of its pharmacologically active metabolite, norzimelidine, was studied in six healthy male volunteers. Three single doses of zimelidine (25 mg and 100 mg orally and 25 mg i.v.) and two single doses of norzimelidine (25 mg orally and i. v.) were given to each volunteer allowing at least seven days between administrations. Plasma concentrations of zimelidine and norzimelidine were determined in serial blood samples by HPLC. Following oral zimelidine peak plasma concentrations of the metabolite were attained about 3 h after dosing. Oral administration of norzimelidine itself resulted in a plasma concentration profile for this compound that was similar to that observed after oral zimelidine. Utilising the plasma concentration data following intravenous infusion of each compound, the elimination half-lives for zimelidine and norzimelidine were calculated to be 5.1 h (range 4.3–6.0) and 15.5 h (range 10.6–22.9) respectively. The total body clearances of the 2 compounds were similar at 0.52 l · min−1 (range 0.26–0.70) for zimelidine and 0.56 l · min−1 (range 0.28–0.83) for norzimelidine. The substantially longer elimination half-life of norzimelidine was apparently the result of a larger volume of distribution (9.4 l · kg−1; range 7.8–11.4) for this metabolite, as compared to zimelidine (3.21 · kg−1; range 1.6–4.9). The calculated bioavailability of zimelidine was 26% (range 9.1–39) after the 25 mg oral dose, and 29% (range 14–46) after the 100 mg dose. The bioavailability of norzimelidine was 66% (range 36–91). However, oral administration of zimelidine resulted in as much or more norzimelidine reaching the systemic circulation, as the oral administration of norzimelidine itself. This is important as a large part of the activity of the drug may be due to the metabolite.
    Materialart: Digitale Medien
    Standort Signatur Erwartet Verfügbarkeit
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  • 3
    Digitale Medien
    Digitale Medien
    Springer
    European journal of clinical pharmacology 18 (1980), S. 321-326 
    ISSN: 1432-1041
    Schlagwort(e): sotalol ; hypertension ; renal impairment ; chronic administration ; pharmacokinetics
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary Ten hypertensive patients with moderate to severe impairment of renal function were treated with sotalol for 5 to 10 weeks (average 6.4 weeks). Dosage was individually titrated (range 80 to 480 mg daily). The drug was given once daily in the morning. In eight patients blood pressure was satisfactorily controlled. Higher steady-state levels were observed than have been reported after similar doses in patients with normal renal function. The apparent first-order elimination rate constant and plasma clearance were significantly correlated with glomerular filtration rate. For an anuric patient, serum half-life was calculated to be 69 h. In relation to the raised plasma levels, side effects were uncommon. Since sotalol is excreted predominantly via the kidney, therapy in patients with impaired renal function should start with a low dose and any increase in dosage should be made carefully. As the anti-hypertensive effect does not appear to be correlated with the plasma level or with tolerance, adjustment of dose should be based on clinical response.
    Materialart: Digitale Medien
    Standort Signatur Erwartet Verfügbarkeit
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  • 4
    Digitale Medien
    Digitale Medien
    Springer
    European journal of clinical pharmacology 18 (1980), S. 225-229 
    ISSN: 1432-1041
    Schlagwort(e): metoprolol ; hypertension ; slow-release preparations ; maximal exercise power ; fatigue
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary The treatment of hypertension with a single daily-dose of a beta-blocker gives rise to high peak-plasma concentrations 1.5 h after ingestion. After slow release-preparations of beta-blockers, the peak concentrations are half those produced by the conventional preparation at the same oral dose. A frequently occurring side-effect of beta-blocker therapy is fatigue. In this study the effect of a single dose of metoprolol 300 mg, 200 mg, 200 mg slow-release and a placebo on maximal exercise power was tested in 6 healthy subjects, 1.5 h and 24 h after ingestion. Maximal exercise power was significantly reduced 1.5 h after ingestion of metoprolol 300 mg and 200 mg. No change was found 1.5 h after 200 mg of a slow-release preparation. The possible reasons for reduced maximal exercise power are discussed. It is concluded that use of a beta-blocker for the treatment of hypertension in a single daily-dose regimen may be a reason to prefer a slow-release preparation.
    Materialart: Digitale Medien
    Standort Signatur Erwartet Verfügbarkeit
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  • 5
    Digitale Medien
    Digitale Medien
    Springer
    European journal of clinical pharmacology 18 (1980), S. 399-401 
    ISSN: 1432-1041
    Schlagwort(e): prazosin ; hypertension ; central monoaminergic neurons ; monoamine metabolites
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary Six hypertensive patients were treated with prazosin up to a final dose of 3–4.5 mg/day. There was a significant reduction of blood pressure. The cerebrospinal fluid (CSF) concentrations of the major metabolites of noradrenaline, dopamine and serotonin were unchanged. This indicates that the antihypertensive effect is not mediated via central monoaminergic neurons as suggested by animal studies.
    Materialart: Digitale Medien
    Standort Signatur Erwartet Verfügbarkeit
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  • 6
    Digitale Medien
    Digitale Medien
    Springer
    European journal of clinical pharmacology 18 (1980), S. 423-428 
    ISSN: 1432-1041
    Schlagwort(e): pyridostigmine ; myasthenia gravis ; pharmacokinetics ; bioavailability ; plasma levels
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary The pharmacokinetics of pyridostigmine was evaluated after intravenous injection in two healthy male volunteers and after oral administration to five subjects. Plasma concentrations of pyridostigmine were determined after ion pair extraction from plasma and analysis by gas chromatography — mass spectrometry with chemical ionization, using d6-pyridostigmine as internal standard. Degradation of pyridostigmine in vitro was compensated for by use of the deuterated internal standard and by rapid cooling and separation of plasma after blood sampling. After intravenous administration of pyridostigmine 2.5 mg the plasma elimination half-life was 1.52 h, the volume of distribution was 1.43 l/kg and the plasma clearance 0.65 l/kg × h. The pharmacokinetic constants were very similar after oral administration of pyridostigmine 120 mg; the elimination half-life was 1.78±0.24 h, the volume of distribution 1.64±0.29 l/kg and the plasma clearance was 0.66±0.22 l/kg × h. The bioavailability was calculated to be 7.6±2.4%. When pyridostigmine was taken together with food, the time to reach the peak plasma concentration was prolonged from 1.7 to 3.2 h. Bioavailability, however, was not influenced by concomitant food intake. “Steady-state” plasma concentrations of pyridostigmine were measured in myasthenic patients on their ordinary dose schedule of cholinesterase inhibitor drugs. More than a seven-fold difference in steady-state plasma concentration was found between patients taking approximately the same daily dose of pyridostigmine.
    Materialart: Digitale Medien
    Standort Signatur Erwartet Verfügbarkeit
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  • 7
    Digitale Medien
    Digitale Medien
    Springer
    European journal of clinical pharmacology 18 (1980), S. 105-108 
    ISSN: 1432-1041
    Schlagwort(e): renin ; angiotensin ; aldosterone ; hypertension ; hypoaldosteronism ; pseudohypoaldosteronism
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary There is increased activity of the renin, angiotensin, aldosterone (RAA) system in infancy and childhood. An inverse relationship between plasma renin, aldosterone and age has been demonstrated. In childhood hypertension due to renovascular disease or pyelonephritic scarring peripheral plasma renin is increased. Renal vein renin measurements in children with renal hypertension have proved valuable in predicting surgical curability of the underlying lesion. The upper limit of normal for the renal venous renin ratio in normotensive children without renal disease is 1.5. Pharmacological blockade of the RAA system has a place in diagnosis and treatment of hypertensive children. The plasma renin aldosterone profile is diagnostically useful in the investigation of salt-wasting disease and can easily distinguish between aldosterone biosynthetic defects and pseudohypoaldosteronism.
    Materialart: Digitale Medien
    Standort Signatur Erwartet Verfügbarkeit
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  • 8
    Digitale Medien
    Digitale Medien
    Springer
    European journal of clinical pharmacology 18 (1980), S. 135-139 
    ISSN: 1432-1041
    Schlagwort(e): hypertension ; labetalol ; propranolol ; renal haemodynamics ; glomerular filtration rate ; blood pressure ; exercise ; renal blood flow
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary The effect of exercise on renal haemodynamics was examined in young patients with mild essential hypertension. Four groups of subjects were studied: 13 normotensive, healthy control subjects, and 15 untreated, 11 propranolol-treated, and 6 labetalol-treated patients. Renal plasma flow (RPF) and glomerular filtration rate (GFR) were measured during four consecutive periods, a pre-exercise control period, two exercise periods with loads of 450 kpm/min and 600 kpm/min, respectively, and a post-exercise control period. In the untreated patients RPF and GFR were lower during exercise than in the normotensive control subjects, whereas no significant differences were found at rest. In the propranolol-treated patients the reduction in RPF and GFR during exercise was more pronounced than in the untreated hypertensives. In the labetalol-treated patients however, RPF and GFR were reduced only to the same degree as in the untreated hypertensives. The reduced renal blood flow in propranolol-treated patients may be attributed to a compensatory increase in sympathetic activity caused by an impaired cardiac response to exercise. The lack of reduction in renal blood flow during labetalol therapy could partly be related to alpha-adrenergic blockade in the renal vascular bed induced by labetalol, and partly to the smaller reduction in cardiac output during labetalol than during propranolol therapy.
    Materialart: Digitale Medien
    Standort Signatur Erwartet Verfügbarkeit
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  • 9
    Digitale Medien
    Digitale Medien
    Springer
    European journal of clinical pharmacology 18 (1980), S. 231-235 
    ISSN: 1432-1041
    Schlagwort(e): molsidomine ; hypertension ; hypotension ; angina pectoris
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary Molsidomine (M), a new long-lasting antianginal compound, was studied in 38 hypertensive patients to assess its antihypertensive properties. Six patients were selected for an acute, single dose comparative trial with placebo over 8 h after treatment. The remaining 32 patients were used in a 1 month trial to study the effect on BP of more prolonged treatment. Systolic, diastolic and mean BP were significantly reduced after a single dose of M 4 mg, and the effect lasted for about 8 h. M also inhibited the hypertensive response to isometric exercise in handgrip tests performed 1 and 8 h after M ingestion. A dose-related decrease in systolic and diastolic BP in the one month trial was also observed. In addition to its antianginal properties, M appears to possess an interesting effect on BP in mildly to moderately hypertensive patients. A fall in BP is also a valuable effect in coronary patients with augmented metabolic demands of the heart.
    Materialart: Digitale Medien
    Standort Signatur Erwartet Verfügbarkeit
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  • 10
    ISSN: 1432-1041
    Schlagwort(e): hypertension ; nifedipine ; beta-adrenoceptor blockade ; hypotensive action ; adverse effects ; combination therapy
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary The antihypertensive effect of nifedipine (10–20 mg t.i.d.) given alone, or in combination with a beta-adrenoceptor blocking drug, was related to the observed plasma concentration during one dosage interval at steady-state (Pl-Nifss). The study was carried out as a within-patient comparison of treatment with nifedipine or placebo for 4 weeks. A highly significant reduction in blood pressure was obtained during monotherapy, as well as during combined treatment. The blood pressure reduction when nifedipine was added to beta-adrenoceptor blockade was of the same magnitude as that observed on nifedipine monotherapy. A considerable variation in Pl-Nifss was noted (range: 2–70 ng/ml). No significant correlation was found between the percentage reduction in blood pressure and Pl-Nifss in either of the two groups. There was a close relationship between Pl-Nifss and the concentration found 4 h after the morning dose. Side-effects were common during nifedipine monotherapy and were the reason for discontinuation of treatment in 4 of 18 patients. In contrast, none of the 9 patients on combined treatment dropped-out. In neither of the treatment groups was there any evidence for sodium retention and volume expansion during the first 4 weeks expressed as weight gain or signs of cardiac insufficiency. However, in 13 patients who continued on long-term treatment for 3–14 months, a definite need for concomitant diuretic therapy was found. The results indicate that nifedipine is effective in lowering blood pressure in patients with mild to moderate essential hypertension, either when given alone or in addition to beta-adrenoceptor blockade. It appears best tolerated as combination therapy. Long-term treatment requires addition of a diuretic. Pl-Nifss did not seem to be a major determinant of the magnitude of the hypotensive response.
    Materialart: Digitale Medien
    Standort Signatur Erwartet Verfügbarkeit
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  • 11
    Digitale Medien
    Digitale Medien
    Springer
    European journal of clinical pharmacology 18 (1980), S. 375-382 
    ISSN: 1432-1041
    Schlagwort(e): calcium antagonist ; verapamil ; hypertension ; vasodilators ; plasma renin activity ; mode of action ; sodium balance ; fluid balance
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary In 12 in-patients with moderate uncomplicated hypertension, maintained on constant sodium intake for 15 days, single-blind oral administration of verapamil 80–160 mg t. i. d. for 10 days had a significant antihypertensive effect: in the supine position systolic blood pressure decreased from 177±5 to 150±3 mmHg, and diastolic pressure from 111±3 to 96±2 mmHg; standing values were similarly lowered from 171±7 to 143±4 mmHg, systolic, and from 118±4 to 97±2 mmHg, diastolic. The heart rate did not show any significant change (from 79±3 to 77±2 beats/min, supine, and from 92±3 to 87±3 beats/min, upright). The antihypertensive effect was uniform throughout the day, being similar 2, 3, 6 and 8 h after administration of a dose. Dynamic exercise (75–100 watts on a cycle-ergometer) caused identical increases in arterial pressure and heart rate on the last day of placebo and again on the last day with verapamil, but the peak levels of systolic pressure reached during exercise were lower after verapamil than with placebo, because of the lower blood pressure before exercise. Reduction of arterial pressure by verapamil was not accompanied by increased plasma renin activity, or by renal retention of sodium and water: there was a small increase in sodium excretion, at least during the first days of verapamil administration (from 107±15 to 113±15 mEq Na+/day), and a slight significant reduction in body weight (from 74.2±3.7 to 73.5±3.7 kg). It is concluded that oral administration of verapamil significantly lowers blood pressure without simultaneously inducing cardiac stimulation, renin secretion or salt and water retention.
    Materialart: Digitale Medien
    Standort Signatur Erwartet Verfügbarkeit
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  • 12
    Digitale Medien
    Digitale Medien
    Springer
    European journal of clinical pharmacology 24 (1983), S. 127-136 
    ISSN: 1432-1041
    Schlagwort(e): statistical analysis ; nonparametric statistical methods ; bioavailability ; confidence interval ; ANOVA
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary For a two-way cross-over design, which appears to be the most common experimental design in bioavailability studies, 95%-confidence limits for expected bioavailability can be obtained by classical analysis of variance (ANOVA). If symmetry of the confidence interval is desired about zero (differences) or unity (ratios) rather than about the corresponding point estimator, Westlake's modification can be used. Two nonparametric methods and their adaptations to bioavailability ratios are reviewed, one based on Wilcoxon's signed rank test (Tukey), and the other on Pitman's permutation test. The necessary assumptions and the merits of these procedures are discussed. The methods are illustrated by an example of a comparative bioavailability study. A FORTRAN program facilitating the procedures is available from the authors upon request.
    Materialart: Digitale Medien
    Standort Signatur Erwartet Verfügbarkeit
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  • 13
    Digitale Medien
    Digitale Medien
    Springer
    European journal of clinical pharmacology 24 (1983), S. 157-161 
    ISSN: 1432-1041
    Schlagwort(e): hypertension ; cadralazine ; single dose ; dose response curve ; hypotensive action ; prolonged effect ; side effects
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary Cadralazine (ISF 2469) was administered to 24 hypertensive patients in single oral doses of 7.5, 10, 15, 20 and 30 mg, according to a single-blind, placebo-controlled, within-patient change-over design. The study was done in 2 stages: in the first a range including the upper and lower doses was studied (7.5, 15, 30 mg and placebo), and in the second the range of doses was restricted (10, 15, 20 mg and placebo). The drug produced a significant decrease in blood pressure in the supine and standing positions. The decrease became clinically important starting from the 15 mg dose. Its action was still significant 12 h after administration. A significant increase in heart rate was also observed. All the effects were correlated with the dose. Side effects occurred mainly after the 30 mg dose. Thus, cadralazine, in a single oral dose in man, showed good antihypertensive activity starting from the 15 mg dose, and its effect was dose-related, slow in onset and long-lasting.
    Materialart: Digitale Medien
    Standort Signatur Erwartet Verfügbarkeit
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  • 14
    Digitale Medien
    Digitale Medien
    Springer
    European journal of clinical pharmacology 24 (1983), S. 217-220 
    ISSN: 1432-1041
    Schlagwort(e): metoprolol ; pregnancy ; hypertension ; kinetics ; pre-eclampsia
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary The disposition of oral metoprolol was studied in 5 women during the last trimester of pregnancy and 3 to 5 months after delivery. After a single oral dose of 100 mg the individual peak plasma concentration in the pregnant state was only 20–40% of that after pregnancy. The plasma half-lives of metoprolol were about the same during (average 1.3 h) and after pregnancy (average 1.7 h). By contrast, the area under the plasma concentration versus time curve was much smallerduring (mean 262 nmol/l×h) thanafter (mean 1298 nmol/l×h) pregnancy, resulting in an average apparent oral clearance (Clo) of metoprolol that was 4.4times higher during (362 ml×kg−1 body-weight×min−1) than after pregnancy. The increased Clo in pregnancy is assumed to be due to enhanced hepatic metabolism of the drug. The possible clinical consequence of the difference in the disposition of metoprolol is discussed.
    Materialart: Digitale Medien
    Standort Signatur Erwartet Verfügbarkeit
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  • 15
    Digitale Medien
    Digitale Medien
    Springer
    European journal of clinical pharmacology 24 (1983), S. 307-314 
    ISSN: 1432-1041
    Schlagwort(e): endralazine ; hypertension ; blood pressure ; heart rate ; renal clearance ; plasma renin activity ; plasma aldosterone
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary The effects of endralazine, a new antihypertensive hydrazinopyridazine derivative, on heart rate, mean blood pressure (mBP), glomerular filtration rate (GFR), effective renal plasma flow (CPAH), urine volume (V), the clearance of Na, K, urea (Ur) and uric acid (UA), plasma renin activity (PRA) and plasma aldosterone (PA) were studied in hypertensive patients after a single oral dose of 10–15 mg, and after 8–17 days of treatment with daily doses of 15–90 mg. In the acute experiments, heart rate increased by 27%, mBP decreased on average by 17% and GFR by 33% and CPAH fell by only 5%. Urine volume and electrolyte clearance were also depressed. There was a significant increase in PRA and PA. The fall in GFR correlated directly with mBP, CPAH and the product (mBP×CPAH). The logarithms of the Na clearance and V were correlated with GFR and mBP. The logarithms of the fractional excretion of Na and water also correlated with mBP, suggesting that tubular reabsorption of sodium and water may be affected by change in mBP. The fractional potassium excretion correlated directly with CPAH and ln PA. In contrast, on sustained daily treatment, mBP was less depressed (9%), but GFR increased strikingly by 27% and CPAH by 46%. The body weight increased by 4.5% as a consequence of salt and water retention. GFR was correlated with CPAH, the product (mBP×CPAH) and the increase in body weight. Thus, the improvement in GFR and effective renal plasma flow observed under these conditions may be due, in part, to volume expansion. However, a direct renal vasodilating effect of the drug appears to be the more important determinant.
    Materialart: Digitale Medien
    Standort Signatur Erwartet Verfügbarkeit
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  • 16
    Digitale Medien
    Digitale Medien
    Springer
    European journal of clinical pharmacology 24 (1983), S. 579-583 
    ISSN: 1432-1041
    Schlagwort(e): indapamide ; hypertension ; baroreflex ; vascular reactivity ; heart rate ; blood pressure change
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary The effect of chronic treatment with indapamide on blood pressure (BP), baroreceptor sensitivity (BRS) and vascular reactivity (VR) were investigated in 10 patients with essential hypertension. After 3 months of therapy with indapamide 2.5 mg/d the mean arterial pressure (MAP) had decreased from 135±6 to 112±2 mmHg (p〈0.001); the heart rate (HR) had not changed, VR had decreased from 6.1±1.2 to 4.8±1.8 (pg·min·kg)−1 (p〈0.05), and BRS had increased from 8.3±3.7 to 12.2±5.3 ms/mmHg (p〈0.005), with a leftshift of the relationship between BP and heart period. An inverse correlation was found between the pre-treatment systolic blood pressure and the change in baroreceptor sensitivity after indapamide (r=0.59; p〈0.05). In conclusion, chronic treatment with indapamide enhances BRS and resets the reflex. The resetting may account for the lack of tachycardia at rest observed after treatment with indapamide. The mechanism by which indapamide interferes with the baroreceptor reflex requires further investigations.
    Materialart: Digitale Medien
    Standort Signatur Erwartet Verfügbarkeit
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  • 17
    Digitale Medien
    Digitale Medien
    Springer
    European journal of clinical pharmacology 24 (1983), S. 791-796 
    ISSN: 1432-1041
    Schlagwort(e): furosemide ; bioavailability ; diuretic effect ; urine sodium ; urine potassium ; power of ANOVA ; tablet formulations ; urinary flow rate ; normal volunteers
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary The relative bioavailability and diuretic effect of 2 commercially available tablet preparations of furosemide 40 mg was examined in 10 healthy male volunteers. A close linear relationship between the urinary excretion rate of furosemide and the rate of sodium ion excretion in urine and/or flow rate of urine was demonstrated. There were no significant differences in the urinary excretion of furosemide, sodium and potassium ions or urinary volume following the oral doses. The difference in drug content affected the urinary recovery of furosemide over 24 h but had no effect on the pharmacological response. The analytical power of ANOVA using the various parameters of the responses to furosemide was no lower than when the parameters of urinary excretion of furosemide were used.
    Materialart: Digitale Medien
    Standort Signatur Erwartet Verfügbarkeit
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  • 18
    Digitale Medien
    Digitale Medien
    Springer
    European journal of clinical pharmacology 25 (1983), S. 143-144 
    ISSN: 1432-1041
    Schlagwort(e): hypertension ; nifedipine ; plasma concentration ; blood pressure response
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Materialart: Digitale Medien
    Standort Signatur Erwartet Verfügbarkeit
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  • 19
    Digitale Medien
    Digitale Medien
    Springer
    European journal of clinical pharmacology 25 (1983), S. 237-241 
    ISSN: 1432-1041
    Schlagwort(e): triamterene ; bioavailability ; pharmacokinetics ; metabolism ; hydroxy triamterene sulphate ; urinary excretion ; i.v. administration ; first-pass-effect
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary With a new formulation, which made intravenous infusion of triamterene (TA) possible, plasma levels and urinary excretion rates of TA and its main metabolite (OH-TA-ester) were measured in a randomized, cross-over trial in 6 healthy volunteers given triamterene 10 mg i.v. and 50 mg p.o. TA and OH-TA-ester were determined by densitometric measurement of native fluorescence after thin layer chromatography. Distribution volumes of the central compartment of TA and OH-TA-ester were 1.49 l/kg and 0.11 l/kg, respectively. Terminal half-lives were 255 min for TA and 188 min for OH-TA-ester after i.v. administration. For TA total plasma clearance was 4.5 l/min and renal plasma clearance 0.22 l/kg. The formation of OH-TA-ester was very rapid and the concentration of the metabolite exceeded that of TA at all times. After i.v. administration the urinary recovery of TA and OH-TA-ester was 4.4% and 50.9%, respectively. The bioavailability of TA was 52%, corresponding to absorption of 83%. TA is partly eliminated by a first-pass-effect. The main metabolite of TA is OH-TA-ester, which is pharmacologically active.
    Materialart: Digitale Medien
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  • 20
    ISSN: 1432-1041
    Schlagwort(e): furosemide ; hypertension ; plasma renin activity ; plasma adrenaline ; plasma noradrenaline ; body fluid loss ; diuretic response
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary To evaluate the role of adrenergic mechanisms in the acute response of renin to furosemide, plasma renin activity (PRA) and plasma catecholamine concentrations were measured for 3 h after i.v. administration of furosemide 1 mg/kg to 8 patients with mild essential hypertension. Furosemide induced a prompt and long-lasting increase in renin, with PRA more than doubled at all times. The increase in PRA within the first 30 min paralleled the peak increases in urinary water and sodium flow rates, and significant decreases in plasma volume and central venous pressure. There was no change in plasma catecholamine concentrations. Plasma noradrenaline was increased significantly at 60 min and adrenaline at 90 min, once furosemide had induced a marked loss of body-fluid and ∼65% decrease in central venous pressure. Both catecholamines remained elevated until the end of the study, whereas urinary water and sodium flow rates had returned to their pre-treatment values by 150 min. Mean blood pressure was essentially unchanged throughout the study, whereas heart rate increased significantly after 90 min. The findings suggest that in mildly hypertensive patients adrenergic mechanisms are not involved in the initial renin response to furosemide, but they come into play later, probably as a result of reflex sympathetic activation triggered by marked volume depletion.
    Materialart: Digitale Medien
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  • 21
    Digitale Medien
    Digitale Medien
    Springer
    European journal of clinical pharmacology 25 (1983), S. 307-312 
    ISSN: 1432-1041
    Schlagwort(e): ketanserin ; hypertension ; blood pressure ; plasma noradrenaline ; exercise ; orthostatic reflexes
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary Ketanserin is a new, specific serotonin receptor blocking agent, which causes vasodilatation, presumably by an action on the vascular wall. The antihypertensive response to ketanserin 40 mg twice daily as monotherapy was assessed in 8 patients with essential hypertension. The investigation was an 8 week, double-blind, cross over study, which also included measurements during isometric (handgrip) and dynamic exercise (bicycle ergometry), as well as determination of plasma catecholamines and ketanserin. Ketanserin caused a reduction of supine and standing systolic and diastolic blood pressure (BP) during rest and a slight bradycardia. Although there was attenuation of the pressor response to handgrip, treatment with ketanserin did not really affect the changes in BP or heart rate during exercise, i.e. the base-line differences remained the same. There was no significant correlation between the effect on BP and the plasma level of ketanserin. The changes in BP produced by ketanserin showed little correlation with the initial levels of plasma catecholamines or with alterations in those levels. Although the results did not indicate direct interference by ketanserin with sympathetic tone, the lack of reflexogenic tachycardia, as well as the lack of increase in plasma noradrenaline during hand grip, indicates at least some modulation of autonomic function. It is concluded that ketanserin lowers BP in essential hypertension without interference with cardiovascular reflexes during standing or exercise, and that the compound may offer an alternative approach in the treatment of hypertension.
    Materialart: Digitale Medien
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  • 22
    Digitale Medien
    Digitale Medien
    Springer
    European journal of clinical pharmacology 25 (1983), S. 449-453 
    ISSN: 1432-1041
    Schlagwort(e): canrenone ; pharmacokinetics ; plasma level ; bioavailability ; urinary excretion ; spironolactone
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary Five healthy male volunteers received canrenoate-K 200 mg (Sincomen® pro injectione) by intravenous injection and one week later spironolactone 200 mg (Sincomen®-100) orally. Plasma levels and urinary excretion of unchanged canrenone were determined up to 24 h by a specific HPLC method. Following intravenous administration, the maximum plasma level of 2066±876 ng/ml was found after 29±15 min and thereafter the concentration declined with a half-life of 3.7±1.2 h. Total clearance was 4.2±1.7 ml/min·kg. After oral ingestion, the maximum concentration of 177±33 ng/ml was observed at 4.4±0.9 h. The absolute bioavailability of canrenone was 25±9%. Within 24 h, respectively 0.4 and 0.6 mg, canrenone were excreted by the kidney after intravenous and oral administration. The half-life of elimination was 4.9±1.8 h (i.v.) and 3.9±1.2 h (p.o.).
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  • 23
    Digitale Medien
    Digitale Medien
    Springer
    European journal of clinical pharmacology 25 (1983), S. 571-575 
    ISSN: 1432-1041
    Schlagwort(e): beta-blocker ; felodipine ; calcium antagonist ; hypertension ; vasodilator ; side effects ; plasma levels ; metoprolol ; propranolol
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary In a double-blind, cross-over trial, 10 men with primary hypertension, not adequately controlled with a β-blocker alone, were also given felodipine or placebo for periods of one week. Placebo was administered single-blind for 2 weeks and 1 week, respectively, before randomization and between treatments. The dose of felodipine ranged from 6.25 mg to 25 mg. The addition of felodipine resulted in a pronounced (20%), statistically significant reduction in blood pressure (BP) and a small but significant increase in heart rate (HR). The effects were seen within 1–2 h and were maximal after 3–4 h. During steady state treatment the duration of BP reduction was at least 12 h. No orthostatic reaction was seen. There was a significant correlation between the plasma concentration of felodipine and change in BP. The most frequently reported side-effects were headache and ankle oedema, the latter probably being due to pronounced pre-capillary vasodilatation. There was no weight increase and thus no indication of general water retention. No clinically significant change in laboratory variables and no influence on the P-Q time were seen. Thus, felodipine in combination with a β-blocker seems to be a useful addition to the treatment of hypertensive patients whose BP is not adequately controlled with a β-blocker alone.
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  • 24
    ISSN: 1432-1041
    Schlagwort(e): prizidilol ; hypertension ; exercise test ; beta-blockade ; vasodilatation ; haemodynamic effects ; vascular tone ; muscle blood flow
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary Fourteen men with moderately severe essential hypertension were treated with prizidilol hydrochloride 400–700 mg once daily (mean±S.D. 612±56 mg/day). The study was open and ambulatory, with an initial placebo period followed by dose titration of prizidilol. Prior to treatment and during optimal control of blood pressure cardiovascular adaptation was examined in a submaximal exercise test. Plethysomographic assessment of vascular flow, resistance and tone in the calf musculature during supine rest and during maximal vasodilatation was also performed. A highly significant reduction in systolic (from 164±4.5 to 141±2.7 mmHg; p〈0.001) and diastolic blood pressure (from 105±1.6 to 87±1.3 mmHg; p〈0.001) at supine rest was noted during therapy with prizidilol. There was no significant change in heart rate. Systolic pressure in the standing position was reduced (from 159±4.2 to 139±2.9 mmHg; p〈0.001) and so was the diastolic pressure (from 111±2.5 to 95±1.9 mmHg; p〈0.001). The heart rate in the standing position was significantly increased compared to supine rest in the placebo period and during optimal treatment with prizidilol. The β-adrenoceptor blocking properties of prizidilol were apparent as a reduction in the exercise-induced heart rate response at even the lowest work load. During prizidilol therapy an increase in resting calf muscle blood flow was found from 3.1±1.5 ml/min·100 ml to 4.3±2.1 ml/min·100 ml (p〈0.025). Vascular resistance and vascular tone were significantly reduced. No change regarding blood flow or resistance during maximal vasodilatation was noted. It is considered that prizidilol has a clear antihypertensive effect combining β-receptor blocking and vasodilator properties.
    Materialart: Digitale Medien
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  • 25
    ISSN: 1432-1041
    Schlagwort(e): atenolol ; hypertension ; plasma renin activity ; pharmacokinetics ; pharmacodynamic effects
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary To show whether repeated administration of atenolol for several days would influence its pharmacokinetic parameters and the extent and duration of the pharmacologic responses, the plasma level of atenolol and changes in heart rate, blood pressure and plasma renin activity were measured in 12 hypertensive patients at various times of day (9 a. m., 12 noon, 3 p. m. and 7 p. m.) after oral administration of the first dose of atenolol 100 mg, again during the 7th and 14th days of continued once-daily administration of the same dose, and finally during the three days following withdrawal of the drug. The peak plasma concentration of atenolol (about 600 ng/ml) was found 3 h after administration of the first dose, and measurable amounts (50–70 ng/ml) were found after 24 h. None of the pharmacokinetic characteristics were changed by administration of a single daily dose for two weeks. After withdrawal of the drug, detectable amounts of atenolol were found in plasma for at least 48 h. The first dose of atenolol caused prompt (3 h) and prolonged (up to 24 h) lowering of supine and standing systolic and diastolic blood pressures, slowing of supine and standing heart rate, reduction of the blood pressure and heart rate responses to dynamic exercise, and a decrease in plasma renin activity. The extent and time-course of all these responses were not influenced by repeated once-daily administration of the 100 mg dose for two weeks. Most of the effects continued during the withdrawal days, the lowering of blood pressure being somewhat more prolonged than the slowing of heart rate. It is concluded that a once-daily dose of atenolol 100 mg decreases blood pressure and heart rate throughout the following 24 h, without excessive daily fluctuation in its effects, and without signs of tolerance or accumulation.
    Materialart: Digitale Medien
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  • 26
    Digitale Medien
    Digitale Medien
    Springer
    European journal of clinical pharmacology 18 (1980), S. 415-418 
    ISSN: 1432-1041
    Schlagwort(e): diclofenac ; acetyl salicylic acid ; intravenous bolus administration ; oral administration ; interaction ; bioavailability
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary Previous studies have shown that aspirin interacts with orally administered diclofenac sodium, causing reduced peak concentrations, lower levels and decreased areas under curves. In this study, diclofenac sodium was administered orally and intravenously with and without aspirin, to 6 healthy female volunteers. After intravenous dosing both plasma levels and areas under curves were significantly reduced although none of the rate constants was affected. The volume of distribution of diclofenac was increased as was the plasma clearance. Oral administration with aspirin also resulted in lower plasma levels, particularly peak levels, and areas under curves. Comparison of AUC's for both modes of administration with and without aspirin suggested that lower levels after oral administration were not due to impaired absorption. These observations are best explained by decreased protein binding and increased biliary excretion of diclofenac in the presence of salicylate.
    Materialart: Digitale Medien
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  • 27
    Digitale Medien
    Digitale Medien
    Springer
    European journal of clinical pharmacology 17 (1980), S. 239-241 
    ISSN: 1432-1041
    Schlagwort(e): timolol ; hypertension ; dose ranging ; double-blind trial
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary Nine previously untreated patients with mild-moderate hypertension were included in a dose-ranging double-blind trial to determine the effectiveness of daily versus thrice daily timolol administration. In 8 patients control of blood pressure was equally effective though with significantly lower heart rate achieved in the once daily group. One patient was not satisfactorily controlled on the daily regimen demonstrating that many but not all hypertensives can be controlled with daily administration of timolol.
    Materialart: Digitale Medien
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  • 28
    Digitale Medien
    Digitale Medien
    Springer
    European journal of clinical pharmacology 17 (1980), S. 309-315 
    ISSN: 1432-1041
    Schlagwort(e): valproic acid ; sodium valproate ; suppositories ; micro-enemas ; steady-state concentration ; absorption ; bioavailability
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary Rectal and oral absorption of valproic acid and its sodium salt by man were compared to explore the possibility of rectal administration of the drug. The plasma concentration of valproic acid was measured by gas chromatography after a single oral dose of sodium valproate 600 mg, and after single rectal doses of sodium valproate 600 mg and valproic acid 520 mg, in a cross-over study in 7 volunteers. The rectal dosage forms included fatty suppositories and aqueous solutions. Compared with oral administration, rectal absorption of sodium valproate from an aqueous micro-enema was fast and complete. The free acid was absorbed more rapidly from fatty suppositories than was the sodium salt. The absorption rate from the rectum increased with the dose of valproic acid. Both findings are consistent with a diffusion — absorption mechanism based on the pH-partition hypothesis. Differences in the chemical composition of the fatty suppository base were not reflected in differences in absorption rate and relative bioavailability. No essential difference in absorption rate was observed if volunteers remained lying or sitting during the experiment. Rectal dosing with valproic acid 520 mg dissolved in 4 ml suppositories, twice a day resulted in steady-state plasma concentrations of 50 to 100 µg · ml−1, within the therapeutic range.
    Materialart: Digitale Medien
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  • 29
    Digitale Medien
    Digitale Medien
    Springer
    European journal of clinical pharmacology 17 (1980), S. 379-384 
    ISSN: 1432-1041
    Schlagwort(e): theophylline ; aminophylline ; obstructive lung disease ; microcrystalline ; bioavailability ; pharmacokinetics
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary Variation in the systemic disposition of theophylline after ingestion of a new microcrystalline product (Theolair®) has been investigated in 7 hospitalized patients with generalized obstructive lung disease. Disposition (absolute bioavailability) was determined by comparing in the same patients the areas under the serum concentration-time curves after a single oral dose of microcrystalline theophylline and after an intravenous infusion of aminophylline. Oral absorption appeared to be fast. The half-life of absorption was 19±9 min (mean±SD). Maximal serum concentrations reached after 100±30 min were found to be in a rather narrow range: 9.8±2.5 mg · 1−1. The absolute bioavailability of the microcrystalline preparation was high and it showed only small variation: 102.7±10.2% of the dose. Relevant pharmacokinetic parameters (half-life of elimination, volume of distribution and total body clearance) were determined after both routes of administration. Individual dosage regimens required to obtain a therapeutic serum concentration were calculated for each individual patient on the basis of the observed pharmacokinetic parameters.
    Materialart: Digitale Medien
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  • 30
    Digitale Medien
    Digitale Medien
    Springer
    European journal of clinical pharmacology 18 (1980), S. 391-394 
    ISSN: 1432-1041
    Schlagwort(e): propranolol ; hypertension ; beta-adrenergic blockade ; exercise heart rate ; pharmacokinetics
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary The pharmacokinetics of propranolol in 16 hypertensive patients was compared after the first oral dose of 80 mg and during chronic treatment with 80 mg bd. The degree of beta-adrenergic blockade was estimated by the reduction in maximal exercise heart rate. No significant change in plasma half-life occurred and there was no correlation between the mean steady-state propranolol concentration and beta-adrenergic blockade or antihypertensive effect. A linear relationship was observed between the decrease in blood pressure and the reduction in heart rate during maximal exercise. Therefore, the antihypertensive effect of propranolol can be explained by its peripheral beta-adrenergic blocking properties.
    Materialart: Digitale Medien
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  • 31
    Digitale Medien
    Digitale Medien
    Springer
    European journal of clinical pharmacology 24 (1983), S. 15-19 
    ISSN: 1432-1041
    Schlagwort(e): hypertension ; mianserin ; clonidine ; methyldopa ; depression ; α2 receptors ; interaction
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary The concurrent administration of tricyclic antidepressants has been shown in man to result in a clinically significant impairment of the antihypertensive effect of clonidine. This interaction is thought to be related to competition for central α2 receptors where clonidine acts as an agonist and the tricyclics act as antagonists. Although it seems to cause less cardiovascular effects than tricyclic antidepressants, the tetracyclic antidepressant, mianserin also has been reported to be an α receptor antagonist and may, therefore, also interfere with the antihypertensive activity of centrally-acting drugs. This study investigates the effects of acute and chronic mianserin administration in patients with essential hypertension established on long term treatment with either clonidine or methyldopa. The first dose of mianserin was not associated with an increase in blood pressure and during a further two weeks of mianserin therapy there were no significant alterations in blood pressure, supine or erect. Similarly, mianserin did not alter heart rate either after acute or after chronic administration. Mianserin itself had a sedative effect but there was no interference with the sedation attributable to clonidine or methyldopa. Mianserin caused no reduction in salivary flow and did not influence the reduced saliva production caused by clonidine. Both clonidine and methyldopa are associated with a reduction in sympathetic outflow but there was no evidence in this study of any further change in plasma noradrenaline or 24 h urinary catecholamine excretion. This study demonstrates that if mianserin is given acutely or chronically, it does not interfere with the effects of the centrally acting antihypertensive drugs, clonidine and methyldopa. Mianserin may therefore be a suitable antidepressant for patients receiving these antihypertensive agents if drug treatment for depression is indicated.
    Materialart: Digitale Medien
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  • 32
    Digitale Medien
    Digitale Medien
    Springer
    European journal of clinical pharmacology 24 (1983), S. 103-108 
    ISSN: 1432-1041
    Schlagwort(e): dexamethasone ; bioavailability ; pharmacokinetics ; ‘first-pass’ effect ; pre-systemic elimination
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary The pharmacokinetics and oral biovailability of dexamethasone were studied in 6 patients with neurological disease being treated with high dosages of the drug. A specific high performance liquid chromatographic assay was used to measure dexamethasone concentrations. Unlike the previously published mean figure of 0.78 for the oral bioavailability of the drug given in single doses to healthy volunteers, the mean bioavailability of dexamethasone in the patients studied was 0.53±SD 0.40. It appeared more likely that this incomplete bioavailability was due to presystemic elimination than to poor absorption. The intravenous clearance of the drug was relatively high (0.4902±SD 2291 l kg−1, approximately 65% of expected hepatic plasma flow), the oral clearance higher (2.5804±SD 3.2181 l kg−1 h−1) while the absorption rate constant (4.8729±8.4998 h−1), suggested rapid absorption after oral administration. Prior phenytoin and possibly prior dexamethasone therapy is likely to have contributed to the higher clearance values of the drug in these patients than the values reported in healthy volunteers after single dose studies.
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  • 33
    Digitale Medien
    Digitale Medien
    Springer
    European journal of clinical pharmacology 24 (1983), S. 1-5 
    ISSN: 1432-1041
    Schlagwort(e): hypertension ; nifedipine ; calcium antagonists ; beta-blockers ; vasodilators ; diuretics
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary Nifedipine has been assessed as a possible alternative to other third line drugs in the management of patients with difficult to control hypertension. A group of 20 patients whose blood pressure was unsatisfactory on a 3 drug regimen had their third drug stopped and after a 2 week period nifedipine was added to their beta-blocker plus diuretic therapy. Eleven became normotensive on 30 mg nifedipine daily and a further 6 on 60 mg daily; giving on overall success rate of 85%. This result was achieved with a reduction in side effects and an absence of any haemodynamic or metabolic complications.
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  • 34
    Digitale Medien
    Digitale Medien
    Springer
    European journal of clinical pharmacology 24 (1983), S. 301-305 
    ISSN: 1432-1041
    Schlagwort(e): endralazine ; hypertension ; pindolol ; peripheral vasodilator ; acetylator phenotypes ; antinuclear antibodies ; SLE-syndrome ; side-effects
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary Nineteen out-patients with moderate to severe essential hypertension were treated daily for 3 years, with an average dose of 13 mg endralazine, a new peripheral vasodilator, in free combination with pindolol 3×5 mg. The blood pressure showed a statistically significant reduction from 172/110 mmHg to 154/92 mmHg after treatment for 3 weeks. Tachyphylaxis was not observed during the 3 year period. Oedema was the most frequent side-effect, but it disappeared spontaneously. No difference in efficacy and tolerance between slow and fast acetylators was found. Only 2 patients developed a weak positive antinuclear antibody titre, which disappeared spontaneously from one during continued treatment. No clinical evidence of a systemic lupus erythematosus-like syndrome was noted. It is concluded that the differences between endralazine and hydralazine in dosage and metabolism may explain the lower immunogenic activity of endralazine.
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  • 35
    Digitale Medien
    Digitale Medien
    Springer
    European journal of clinical pharmacology 24 (1983), S. 353-356 
    ISSN: 1432-1041
    Schlagwort(e): oxmetidine ; pharmacokinetics ; bioavailability ; plasma half-life ; clearance ; oral dose ; i.v. dose
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary The plasma concentration curves and urinary excretion of oxmetidine after administration of single i.v. (100 mg) and oral (200 mg) doses have been studied in 11 patients with peptic ulcer disease. The mean bioavailability of the drug was 70% (range 53–91%). After intravenous administration, the mean plasmat 1/2β was 3.0 h, the mean apparent volume of distribution 0.7 l/kg, the mean total plasma clearance 12.3 l/h and the mean plasma renal clearance was 0.7 l/h. Following intravenous and oral administration an average of 6% and 3%, respectively, of unchanged drug was found in the urine. The plasma concentration curve after oral administration in most patients exhibited two maxima, with peak concentrations appearing between 45 and 210 min after dosing.
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  • 36
    Digitale Medien
    Digitale Medien
    Springer
    European journal of clinical pharmacology 25 (1983), S. 481-490 
    ISSN: 1432-1041
    Schlagwort(e): propranolol ; pharmacokinetics ; pregnancy ; hypertension ; naphthoxylactic acid
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary The pharmacokinetics of propranolol (P) and its major metabolites, propranolol glucuronide (PGLUC), 4-hydroxypropranolol (4OHP), 4-hydroxypropranolol glucuronide (4OHPGLUC) and naphthoxylactic acid (NLA), (Walle et al. 1972) were determined, whenever possible, in the first, second and third trimesters of pregnancy in thirteen patients and also when these patients were at least three months post-partum. No correlations were found between the mean arterial blood pressure (post-therapy) or the fall in blood pressure as a result of the P therapy (p〉 〉0.05) and P dose, peak P plasma concentrations, peak 4-hydroxypropranolol (4OHP) plasma concentrations or peak (P plus 4OHP) plasma concentrations. However, a positive nonlinear relationship was found between the daily P dose (independent variable) and peak P plasma concentrations over the daily dose range 30–160 mg/day. The elimination half-lives of NLA for patients in the third trimester of pregnancy were significantly shorter (p=0.072, df=13) than those when the patients were at least three months post-partum. Also, the areas under the plasma level-time curves of NLA were significantly less (p〈0.05, df=13) for patients in the third trimester of pregnancy than when these patients were at least three months post-partum. The results of this study indicate that the pharmacokinetics of P, PGLUC, 4OHP and 4OHPGLUC are not significantly altered by pregnancy. However, the kinetics of NLA do appear to be altered. The formation of NLA by N-dealkylation of P and further oxidation, appears to be competitively inhibited by unidentified substances, perhaps endogenous steroids, especially in the third trimester when compared to at least three months post-partum.
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  • 37
    ISSN: 1432-1041
    Schlagwort(e): pinacidil ; hypertension ; side effects ; pharmacokinetics ; fluid retention ; retarded release tablet
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary In an open study increasing doses of a retarded tablet formulation of pinacidil were given twice daily for four weeks to 9 patients with untreated essential hypertension (WHO I–II). In all patients a decrease in diastolic blood pressure to below 100 mmHg, or a fall exceeding 15 mmHg, was obtained 2 h after tablet intake (p〈0.02), but in only two patients was the effect maintained after 10 hours (n.s.). At a mean serum concentration of 100 ng/ml 2 h after pinacidil 30 mg, the mean blood pressure had decreased by 14 and 12.7 mmHg in the supine and erect positions, respectively (p〈0.05). In contrast, mean blood pressure 10 h after the same dose was unchanged, when the mean serum concentration was 47.5 ng/ml. No change in heart rate was observed. Pharmacokinetic and pharmacodynamic investigations showed a tendency towards a more gradual and longer lasting antihypertensive effect and serum concentration-time curve after the retarded tablet than the previous tablet. Pinacidil 40 mg in the retarded tablet reduced mean blood pressure and increased heart rate for at least 8 h. There was a linear correlation between the serum concentration and the changes in mean blood pressure, and between the changes in mean blood pressure and in heart rate. There was no indication of tachyphylaxis. A serum level of 50 ng/ml of pinacidil appeared to be the minimal effective concentration. The side effect consisted of fluid retention, and the body weight increased by 1.0 kg (p〈0.05); four patients complained of oedema. Therapy was discontinued in one patient after a fainting episode following an increase in the dose. Thus, pinacidil was able to lower blood pressure during monotherapy for 4 weeks provided that an adequate serum concentration was achieved. The present retarded tablet formulation is not suitable for b. d. dosing. The tendency towards fluid-retention suggests that pinacidil should be used in combination with a diuretic.
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  • 38
    Digitale Medien
    Digitale Medien
    Springer
    European journal of clinical pharmacology 25 (1983), S. 689-693 
    ISSN: 1432-1041
    Schlagwort(e): amiodarone ; bioavailability ; calculation ; linear pharmacokinetics ; absorption
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary Methods for estimating the bioavailability of drugs with long elimination half-lives are examined. Provided both absorption and disposition are linear a simple linear regression method is developed which can be used to calculate bioavailability in situations where only an incomplete estimate of the area under the curve (AUC) is available. The regression method and the traditional method of comparing the AUC following an oral dose to the AUC following an i.v. dose were applied to simulated data. It was found that the AUC ratio method works well as long as absorption is complete within the time over which the AUC is computed. The regression method is less precise than the AUC ratio method but is more accurate for drugs with long absorption half-lives. When applied to published data on a beta blocker the two methods produced comparable results. The bioavailability of amiodarone in three human subjects was calculated to be 0.20, 0.44 and 0.98 using the regression method with similar results from the ratio method. It is not possible to estimate the clearance of amiodarone from single dose data.
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  • 39
    ISSN: 1432-1041
    Schlagwort(e): captopril ; propranolol ; sympathetic nervous system ; noradrenaline ; aldosterone ; renin ; angiotensin converting enzyme ; hypertension ; isometric exercise
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary The effects of captopril and propranolol on blood pressure, heart rate and plasma noradrenaline, renin and aldosterone, and on the responses to changes in posture and to isometric exercise were measured in patients with essential hypertension. During placebo administration blood pressure, heart rate and plasma noradrenaline rose on standing and during isometric exercise. The rise in diastolic blood pressure during isometric exercise correlated significantly with the rise in plasma noradrenaline. During captopril treatment blood pressure was significantly lower than during placebo administration when the patients were lying, standing or sitting, but the reduction during isometric exercise was not significant. Plasma renin increased, but heart rate, plasma noradrenaline and plasma aldosterone remained unchanged. The acute changes in blood pressure, heart rate and plasma noradrenaline produced by standing and isometric exercise during captopril treatment were similar to those during placebo administration. During propranolol treatment diastolic blood pressure was significantly lower than during placebo administration when the patients were lying, standing or sitting and during isometric exercise. Heart rate also fell. Plasma noradrenaline during standing, sitting and isometric exercise was significantly greater than during placebo administration. The changes in plasma noradrenaline measured during propranolol treatment with the patients supine were negatively correlated with noradrenaline values obtained during placebo administration: plasma noradrenaline fell in patients with higher, and increased in those with lower, initial concentrations. The expected acute increase in heart rate on standing and during isometric exercise was blunted by propranolol, but the changes in blood pressure and plasma noradrenaline were unaffected. We conclude that in essential hypertension noradrenaline is involved in the pressor response to isometric exercise. Angiotensin converting enzyme inhibition by captopril did not interfere with the responses of the sympathetic nervous system to postural changes and isometric exercise. During propranolol treatment there was no evidence that reduced sympathetic activity was involved in the hypotensive response.
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  • 40
    Digitale Medien
    Digitale Medien
    Springer
    European journal of clinical pharmacology 24 (1983), S. 145-150 
    ISSN: 1432-1041
    Schlagwort(e): nifedipine ; hypertension ; pharmacokinetics ; tablet formulation ; dose-response
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary A tablet formulation of nifedipine was given to 8 hospitalized hypertensive men, W.H.O. stage I or II, mean age 45 years. After an initial placebo test, nifedipine 20, 40 or 60 mg was given in random order at 72-h intervals, in a single administration crossover study. The placebo and the active drug were given at 8 a.m. Blood pressure and heart rate were measured twice by the same observer, every 20 min from 7 to 8 a.m., and then hourly until 8 p.m., first in recumbency and again after 1 min of standing upright. Plasma nifedipine was assayed in samples taken hourly from 8 a.m. to noon, every 2 h from noon to 8 p.m., and 24 and 48 h after drug administration. All 3 doses significantly lowered blood pressure; the fall during recumbency was significantly larger (−18%) and lasted longer (12 h) after 60 mg than after 20 mg (−11% and 7 h). All 3 doses caused a similar increase in heart rate (+29 to +38%), which reached its maximum after 2 h and lasted for 5 h. The maximum plasma concentration and the area under the plasma concentration — time curve were dose-dependent despite large inter-subject variation. Absorption, bioavailability and elimination were linear between the 20 and 60 mg doses. Plasma nifedipine levels were strongly correlated with the concomitant decrease in mean arterial blood pressure (r=0.61,p〈0.001). Four patients experienced mild side effects (headaches, flushes, drowsiness or weakness). This tablet form of nifedipine has a potent antihypertensive action which lasts longer than that of the capsule presentation.
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  • 41
    Digitale Medien
    Digitale Medien
    Springer
    European journal of clinical pharmacology 17 (1980), S. 329-332 
    ISSN: 1432-1041
    Schlagwort(e): reserpine ; hydrochlorothiazide ; pituitary hormones ; gonadal hormones ; hypertension ; serum concentration ; antihypertensive therapy
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary Sex histories and serum samples were obtained from 27 hypertensive men before and after 3 months of therapy with either 100 mg of hydrochlorothiazide or 0.25 mg of reserpine daily. Sera were analyzed for testosterone, dihydrotestosterone, estradiol, luteinizing hormone and prolactin. Both drugs effectively lowered blood pressure. The incidence of impaired sexual performance was low and insignificantly different in the two treatment groups. There were no significant changes in serum hormone concentrations as a result of drug therapy.
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  • 42
    Digitale Medien
    Digitale Medien
    Springer
    European journal of clinical pharmacology 17 (1980), S. 375-378 
    ISSN: 1432-1041
    Schlagwort(e): mebendazole ; echinococcosis ; bioavailability ; absorption ; concomitant eating ; plasma level
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary High oral doses of mebendazole are used experimentally for the treatment of human alveolar and cystic echinococcosis. In order to assess bioavailability of this drug 1.5 g doses were given to 3 volunteers. Measurable plasma concentrations of 17 to 134 nmol/l were found only if mebendazole was given together with a fatty meal. In a patient with cholestasis plasma concentrations were higher than in the 3 normal subjects. In patients on long term treatment the increase in plasma concentration after administration of a 1 g dose varied between 0 and 500 nmol/l. It is concluded that systemic availability of mebendazole is enhanced by concomitant food intake. In view of the large intra- and interindividual variation in plasma concentration, monitoring plasma levels during long term therapy appears advisable.
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  • 43
    Digitale Medien
    Digitale Medien
    Springer
    European journal of clinical pharmacology 17 (1980), S. 409-413 
    ISSN: 1432-1041
    Schlagwort(e): penbutolol ; hypertension ; propranolol ; double-blind crossover comparison ; blood pressure ; heart rate
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary Penbutolol is a potent long-acting non-cardioselective beta-adrenergic blocker with partial agonist activity. A double-blind cross-over comparison of penbutolol given in a single daily dose and propranolol given twice daily in the treatment of ambulant patients with moderate hypertension is described. Fourteen patients completed the study and were treated with each drug for 12 weeks. Penbutolol in daily doses of 20–120 mg and propranolol in daily doses of 80–400 mg produced similar significant reductions in both supine and erect blood pressure. Penbutolol did not reduce heart rate to the same extent as propranolol, in equivalent doses. Penbutolol appears to produce adequate control of moderate hypertension when administered once a day, and this effect appears to be equivalent to divided doses of propranolol. No serious adverse effects were reported, although one patient receiving penbutolol experienced severe eye pains at a dose of 40 mg which resolved on crossing over to treatment with propranolol.
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  • 44
    Digitale Medien
    Digitale Medien
    Springer
    European journal of clinical pharmacology 17 (1980), S. 465-468 
    ISSN: 1432-1041
    Schlagwort(e): paracetamol ; suppository ; tablets ; bioavailability
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary The relative bioavailability of a new paracetamol suppository (Panodil) and tablets in doses of 0.5 and 1 g was investigated in eight healthy subjects. The tablets were absorbed faster and higher peak plasma concentrations were obtained than after the suppositories. The bioavailability of the suppositories was approximately 80% of that of the tablets at both dose levels. There was no indication of capacity-limited elimination at either the two doses investigated.
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  • 45
    ISSN: 1432-1041
    Schlagwort(e): papaverine ; propranolol ; pindolol ; hypertension ; isoprenaline ; haemodynamic effects ; blood pressure
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary The influence of two β-adrenoceptor antagonists, propranolol and pindolol, on the haemodynamic effects of papaverine, isoprenaline and noradrenaline was investigated in 9 male patients with first degree essential hypertension. Propranolol and pindolol were given according to a doubleblind, crossover scheme. Heart rate and blood pressure were measured before and after each treatment. Propranolol 670 µg/kg i. v. reduced the supine and standing systolic blood pressures by 2.3% and 1.6%, respectively. Similarly, the intravenous administration of pindolol 35 µg/kg reduced supine and standing systolic blood pressure by 5.5% and 8.3% respectively (clinically insignificant). Neither drug affected diastolic blood pressure. Following propranolol, there were moderate reductions in supine and standing heart rates, respectively by 24% and 20% (p〈0.001). Similarly, but to a lesser extent, pindolol reduced supine and standing heart rate by 12% and 17% (p〈0.001). The effects of papaverine, which, at 1.5 mg/kg i. v. reduced systolic blood pressure by 5–10% and increased heart rate by 8–15%, were not significantly influenced by the β-blockers. The blood pressure and heart rate responses to isoprenaline, on the other hand, were attenuated or inhibited by both β-blockers. While the β-blockers inhibited the β-adrenoceptor component of noradrenaline, the pressor component of noradrenaline, which is mediated through the α-adrenoceptors, was not influenced by propranolol, but was inhibited after pindolol. It is concluded that pindolol differs qualitatively from propranolol in that it inhibited both the α-and β-adrenoceptor effects of noradrenaline.
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  • 46
    Digitale Medien
    Digitale Medien
    Springer
    European journal of clinical pharmacology 17 (1980), S. 321-328 
    ISSN: 1432-1041
    Schlagwort(e): metoprolol ; hypertension ; pharmacokinetics ; plasma renin ; blood pressure effects
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary Eleven patients were treated for essential hypertension with metoprolol (Selokén®) for more than three months. The time course of changes in blood pressure, pulse rate and plasma renin activity was studied during treatment with an oral maintenance dose of 100 mg twice daily. Significant decreases in pulse rate, diastolic blood pressure and plasma renin activity were observed even after the first dose. The plasma concentration of metoprolol reached equilibrium after the second dose. After the third dose there was no further significant change in blood pressure. There was a significant correlation (p〈0.001) between the initial (after three doses) and final (after 〉90days) effect of metoprolol on blood pressure (r=0.86 and 0.91 for systolic and diastolic blood pressure change, respectively).
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  • 47
    Digitale Medien
    Digitale Medien
    Springer
    European journal of clinical pharmacology 24 (1983), S. 251-253 
    ISSN: 1432-1041
    Schlagwort(e): chlorambucil ; prednimustine ; plasma concentrations ; bioavailability ; pharmacokinetics
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary The pharmacokinetics of chlorambucil has been investigated in a cross over study after oral administration of the free drug (10 mg) and its prednisolone ester (prednimustine, 100 mg). The bioavailability of chlorambucil was about five times lower when given as prednimustine as compared to administration of the free drug. The peak plasma concentration was about twice as high and it was obtained more rapidly when the free drug was given. No intact prednimustine could be detected in plasma.
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  • 48
    Digitale Medien
    Digitale Medien
    Springer
    European journal of clinical pharmacology 24 (1983), S. 563-568 
    ISSN: 1432-1041
    Schlagwort(e): indomethacin ; multi-dose kinetics ; controlled release formulation ; capsule formulation ; bioavailability
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary The kinetics of a controlled release (CR) formulation of indomethacin 75 mg (Indocid-Retard®) given once daily was compared with a conventional 25 mg indomethacin capsule (Indocid®) given 3 times daily for 7 days, to 14 healthy volunteers, using a randomized, cross-over, multiple-dose study design. The following differences in plasma indomethacin profiles after the 2 treatments were observed: average peak concentrations (Cmax) for the CR regimen were higher and the time to peak (Tmax) was significantly delayed. Trough (pre-morning dose) plasma concentrations (Cmin) on Days 2, 5, 6 and 7 were significantly lower after the CR-formulation. No statistically significant differences between preparations for area under the plasma concentration time curve (AUC0–24h) or for renal clearance were observed. Average steady-state plasma concentrations (C p ss ) on Day 7 of the multiple dose regimens averaged 0.477 and 0.427 µg/ml for the 75 mg CR once daily and the conventional 25 mg t.i.d. treatments, respectively. These results show that the bioavailability of the CR and conventional indomethacin formulations under these multiple-dose conditions was not significantly different.
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  • 49
    Digitale Medien
    Digitale Medien
    Springer
    European journal of clinical pharmacology 24 (1983), S. 537-542 
    ISSN: 1432-1041
    Schlagwort(e): morphine ; analgesic activity ; tablets solution ; pharmacokinetics ; bioavailability ; pain score ; dose-response relationship ; chronic pain
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary The steady-state kinetics of morphine given as tablets and solution were compared in 7 cancer patients with chronic pain. There was no accumulation of morphine (20–40 mg) when repeatedly administered every 4 to 6 h. The mean steady-state concentration of morphine during the dose interval varied between 5.9 and 68.4 ng/ml (20.7–240 nmol/l), and was linearly related to the daily dose of morphine. There were no significant differences between the tablets and the solution of morphine with regard to relative oral bioavailability or peak concentration. The time-to-maximum plasma concentrations was significantly longer for the tablets. The pain score profile, assessed by a visual analogue scale during a dose interval, showed a similar pattern after the two oral formulations of morphine. No significant linear relationship between the scores and the plasma concentrations of morphine was observed.
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  • 50
    ISSN: 1432-1041
    Schlagwort(e): metoprolol ; bioavailability ; young ; elderly ; metoclopramide ; probanthine ; gut motility
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary The bioavailability of metoprolol was studied in eight healthy young and seven healthy elderly volunteers. Large interindividual differences in the bioavailability of metoprolol were observed in both groups. However, there was no significant difference in AUC, peak plasma concentration or elimination half-life between young and elderly, but time to peak concentration was significantly longer in the elderly. Pretreatment with metoclopramide had no effect on AUC but caused significant increases in peak concentration and decreases in time to peak concentration in both groups. Probanthine pretreatment (only to the young) resulted in a significant decrease in peak concentration of metoprolol and a significant increase in time to peak concentration but had no effect on the AUC. These results suggest that alterations in gastric emptying and gut motility due to ageing or other drugs have no effect on the overall availability of metoprolol to the systemic circulation but may have significant effects on the time to peak plasma concentration and peak concentration achieved after a single oral dose.
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  • 51
    Digitale Medien
    Digitale Medien
    Springer
    European journal of clinical pharmacology 25 (1983), S. 419-424 
    ISSN: 1432-1041
    Schlagwort(e): dihydrocodeine ; pharmacokinetics ; acid metabolites ; radioimmunoassay ; bioavailability
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary Serum concentrations of dihydrocodeine and its acid metabolites have been determined in seven human volunteers (6 male) who received the drug orally (30 mg and 60 mg) and intravenously (30 mg) on separate occasions, and in twenty-four patients (12 male) receiving 25 mg or 50 mg of the drug intravenously. The concentrations were estimated by radioimmunoassay on reconstituted extracts from serum after an extraction process which effectively separates dihydrocodeine from its polar acidic metabolites. The intravenous data show that dihydrocodeine kinetics followed a two-compartment distribution model. The concentration curves after oral administration indicated relatively rapid absorption with mean peak concentrations at 1.6h–1.8h. The mean half-lives varied between 3.3h–4.5h. From the AUC, the mean bioavailability of orally administered drug was 21% (range 12–34%). The peak levels of the acidic metabolites occurred between 1.8h–2.0h after oral administration and 2.2h–2.5h after i.v. administration, and they were significantly greater after oral administration. The low bioavailability of dihydrocodeine, together with the earlier and higher plasma levels of the acid metabolites after oral administration is suggestive of substantial first-pass metabolism.
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  • 52
    Digitale Medien
    Digitale Medien
    Springer
    European journal of clinical pharmacology 25 (1983), S. 467-473 
    ISSN: 1432-1041
    Schlagwort(e): hydralazine ; heart failure ; pharmacokinetics ; bioavailability ; metabolism ; hypertension ; dapsone ; acetylator phenotype
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary The influence of various disease states, other than hypertension, on the pharmacokinetic behaviour of hydralazine is not completely known. In the present study the pharmacokinetics of oral hydralazine has been evaluated in 7 patients with severe, chronic heart failure, using 8 compensated hypertensives as controls. The pharmacokinetics was evaluated by measuring the plasma concentrations of hydralazine (“apparent” and “real” hydralazine) and hydralazine pyruvate hydrazone, and by assessing acetylator phenotype after a small dose of dapsone. The AUC (area under the plasma concentration curve) following a single, oral 50 mg dose was significantly larger in patients with chronic heart failure NYHA Class III–IV than in patients with essential hypertension without cardiac decompensation. A decreased rate of hepatic elimination of hydralazine is suggested as a major contributory factor to this finding.
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  • 53
    Digitale Medien
    Digitale Medien
    Springer
    European journal of clinical pharmacology 25 (1983), S. 463-466 
    ISSN: 1432-1041
    Schlagwort(e): guanfacine ; hypertension ; phenobarbital ; withdrawal syndrome ; enzyme induction ; pharmacokinetics ; renal insufficiency
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary The unusual observation of a withdrawal syndrome due to guanfacine in a hypertensive patient with chronic renal failure led to a study of the kinetics of the drug in this patient. The principal pharmacokinetic parameters of guanfacine were greatly altered, with extended biotransformation and a decrease in the half-life compared to the values observed in other cases of severe renal insufficiency. Associated treatment with phenobarbital had had a considerable effect, as shown by the results of a further kinetic study 2 months after withdrawal of the phenobarbital. The findings then were in good agreement with reference values which strongly suggests a consequence of the enzyme inducing effect of phenobarbital. Advice about the dosage regimen in such cases is given.
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  • 54
    Digitale Medien
    Digitale Medien
    Springer
    European journal of clinical pharmacology 25 (1983), S. 553-556 
    ISSN: 1432-1041
    Schlagwort(e): Endralazine ; pharmacokinetic ; acetylator phenotype ; bioavailability
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary Endralazine (E), a new hydralazine-like antihypertensive was given intravenously (0.05 mg/kg) to 10 normal volunteers (5 slow and 5 fast acetylators). Plasma levels were fitted to a 3 compartment model and pharmacokinetic parameters (area under curve [AUC 0 ∞ ], clearance, volume of distribution, half-lives) obtained in the usual way. Bioavailabilities of 5 and 10 mg oral doses of E were determined from the AUC 0 ∞ generated in a previous study of oral E given to the same subjects. E had high system bioavailability (73.5–99.1%) suggesting that it was almost completely absorbed without undergoing appreciable first-pass metabolism. Furthermore, dose size and acetylator phenotype did not significantly affect the bioavailability of E. This behaviour contrasts with that of hydralazine where systemic bioavailability was 〈40%, and 2 to 3 times higher in slow acetylators than in fast acetylators. It is concluded that the bioavailability of E is high and not influenced by acetylator phenotype; these properties suggest some clinical advantages for the drug.
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  • 55
    Digitale Medien
    Digitale Medien
    Springer
    European journal of clinical pharmacology 25 (1983), S. 667-672 
    ISSN: 1432-1041
    Schlagwort(e): theophylline ; asthma ; children ; sustained-release ; diurnal ; absorption ; bioavailability
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary The absolute oral bioavailability of a sustained release theophylline tablet (Nuelin-SR250), given 12 hourly was determined in 14 asthmatic children aged 5 to 13 years. In 4 of the patients, mean bioavailability of the fourth dose was 38.9±8.4% and that of the sixth dose was 67.9±25.9% (p〈0.05) in the other ten patients. This suggests steady-state had not been achieved after four doses. In the initial study with 9 patients, a significant diurnal variation in predose plasma theophylline concentrations was observed, as the mean morning predose concentrations were 2.9 fold greater than the mean evening predose concentrations (p〈0.005). Dual peak plasma concentrations occurred in 5 out of the 9 patients. The mechanism of this diurnal variation was investigated in a further 5 asthmatic children (10.8 years ±1.6). Morning and night steady-state plasma theophylline concentrations during a continuous intravenous infusion of aminophylline were not different (14.9±5.3 mg/l vs. 15.6±5.9 mg/l), demonstrating that there was no diurnal variation in the plasma clearance of theophylline. The diurnal variation in predose concentrations with Neulin-SR250 was confirmed with the morning concentrations again being 2.6 fold greater than those in the evening. However, bioavailability was not significantly different for day (09.00–21.00) and night (21.00–09.00) dosing intervals after doses 6 and 7 respectively of Nuelin-SR250. The plasma concentration versus time profiles suggested that the diurnal variation in predose concentrations was due to slower absorption of the evening dose.
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  • 56
    Digitale Medien
    Digitale Medien
    Springer
    European journal of clinical pharmacology 25 (1983), S. 713-715 
    ISSN: 1432-1041
    Schlagwort(e): nifedipine ; hypertension ; calcium antagonist ; plasma renin
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary Nifedipine, a calcium antagonist with a predominant vasodilator action, was evaluated for the treatment of hypertension. A 20 mg-tablet, with a slower absorption and a more sustained blood-level than provided by the 10 mg-capsule was administered to 20 patients. The duration of the trial was 20 weeks. All patients achieved a significant reduction in both systolic (p〈0.05) and diastolic (p〈0.001) blood-pressure (B.P.), but 10 patients were withdrawn before completion of the trial period. Two patients, although achieving a fall in B.P. which was significant, did not reach to target level (〈160/90) on maximal dosage, one patient suffered a stroke due to a cerebral infarct, and seven patients were withdrawn because of side-effects due mainly to vasodilatation. The remaining 10 patients obtained a satisfactory response. In nine patients, who had achieved a satisfactory result, there was no change in plasma renin activity (P.R.A.) during chronic nifedipine administration.
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  • 57
    Digitale Medien
    Digitale Medien
    Springer
    European journal of clinical pharmacology 25 (1983), S. 835-837 
    ISSN: 1432-1041
    Schlagwort(e): tienilic acid ; hydrochlorothiazide ; amiloride ; blood pressure control ; biochemical effects ; serum uric acid ; serum potassium ; prolonged treatment ; hypertension
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary A comparison has been made of arterial pressure and major metabolic parameters during long term treatment with tienilic acid and a hydrochlorothiazide-amiloride combination, using a randomized single-blind study without cross-over. A significant fall in systolic and diastolic blood pressure and no change in most biochemical parameters was observed with both drugs. Serum uric acid concentration was decreased during tienilic acid and was slightly increased whilst subjects took the hydrochlorothiazide-amiloride combination; serum potassium was slightly decreased on tienilic acid. No sign of hepatotoxicity was detected.
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  • 58
    ISSN: 1432-1041
    Schlagwort(e): bufuralol ; hypotensive therapy ; pharmacokinetics ; hypertension ; 1-hydroxybufuralol
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary The relationship between the plasma concentrations of bufuralol and its major hydroxymetabolite (Ro 3-7410) and β-blocking activity was studied in 10 patients with uncomplicated essential hypertension. Blood samples and haemodynamic data were obtained during rest and after a single-level exercise test on a bicycle cycloergometer, prior to and up to 32 h after administration of a single oral dose of bufuralol 30 mg. Bufuralol was rapidly absorbed, following a first-order process with a lag time. The calculated maximal plasma concentration ranged from 44.6 to 200.3 ng/ml. The half-life of bufuralol was 2.75±1.15 h (mean±SD). Up to 50% of the parent drug was transformed into Ro 3-7410, which showed less interpatient variability in concentration and a fairly constant half-life, which was three times longer than that of the parent drug. In general, the heart rate (HR) was slightly decreased, although 2/10 patients showed an initial increase. The resting HR returned to its pre-treatment level within 6 h, the exercise HR took up to 32 h to return to the pre-treatment level. The drug reduced both resting and exercise blood pressure (BP). The former was reduced from 153.0±14.2/93.5±8.5 to 134.5±14.0/77.0±6.8 mmHg (systolic/diastolic BP; mean±SD) with 6 h after treatment. Similarly, the exercise BP was reduced from 199.0±15.2/98.5±8.8 to 171.0±9.9/88.5±8.5 mmHg at the 6th h post-dosing. The BP values had not returned to their pre-treatment levels even 32 h after treatment. Thus, bufuralol and its metabolite Ro 3-7410 induced a long-lasting antihypertensive effect and inhibited the cardio-acceleratory effect of exercise, and there was a good correlation between the pharmacokinetic and pharmacodynamic behaviour of the drug.
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  • 59
    Digitale Medien
    Digitale Medien
    Springer
    European journal of clinical pharmacology 24 (1983), S. 509-515 
    ISSN: 1432-1041
    Schlagwort(e): cibenzoline ; pharmacokinetics ; bioavailability ; urinary excretion ; antiarrhythmic drug ; healthy volunteers
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary The kinetics of cibenzoline (UP 339.01), a new antiarrhythmic drug, was studied after i.v. and oral administration to 5 healthy subjects. Cibenzoline levels in plasma and urine cibenzoline were measured by a GLC method. After i.v. administration, the total clearance was 826 ml · min−1. The fraction of cibenzoline excreted unchanged in the urine was 0.602 and it was correlated with the creatinine clearance. After i.v. and oral administration, the renal clearances were 499 ml · min−1 and 439 ml · min−1, and the half-lives were 4 h 01 min and 3 h 24 min, respectively. The differences were not significant. Availability by the oral route was 0.92, the maximum plasma concentration being observed at 1 h 36 min. The results were compared with those for other antiarrhythmic drugs.
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  • 60
    Digitale Medien
    Digitale Medien
    Springer
    European journal of clinical pharmacology 25 (1983), S. 281-283 
    ISSN: 1432-1041
    Schlagwort(e): dyphylline ; pharmacokinetics ; bioavailability ; drug levels
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary The pharmacokinetics and bioavailability of 3 oral dyphylline preparations, solution (S), regular (R) and sustained release (SR), were studied in 8 healthy subjects (mean age 25 years). A single dose of each preparation, 20 mg·kg−1, was given at one week intervals and multiple serum samples obtained over 24 h. Drug levels were measured by high performance liquid chromatography. No adverse effects were found. The dyphylline half-life for the solution was 2.16±0.18 h and for the tablet 2.59±0.56 h. The mean clearance rate for S was 13.6±1.7 h−1 and volume of distribution 43.0±3.91. Peak concentration (Cmax, µg·ml−1), time of peak (Tmax, h), area under the curve (AUC, µg·ml−1·h) and relative bioavailability (RB, %), were determined for three preparations: The data confirm the short half-life of dyphylline, demonstrate a lack of toxicity for the 20 mg·kg−1 dose and establish bioequivalence for the products studied.
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  • 61
    Digitale Medien
    Digitale Medien
    Springer
    European journal of clinical pharmacology 25 (1983), S. 357-359 
    ISSN: 1432-1041
    Schlagwort(e): pindolol ; bioavailability ; fluorimetric assay ; GLC-ECD assay
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary The absolute oral bioavailability of pindolol has been estimated by two analytical methods, fluorimetry and GLC-ECD. The study was carried out in six healthy subjects who received either i.v. or oral pindolol in random order. The results obtained by both methods were similar and confirm the high bioavailability (about 75%) of pindolol. The present findings are compared with previous publications and emphasize the importance of undertaking bioavailability studies in the same subjects.
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  • 62
    Digitale Medien
    Digitale Medien
    Springer
    European journal of clinical pharmacology 25 (1983), S. 581-583 
    ISSN: 1432-1041
    Schlagwort(e): hypertension ; metoprolol ; hydrochlorothiazide ; drug combination ; adverse reactions
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary In 27 hypertensive patients whose blood pressure could not be adequately controlled with 200 mg metoprolol Durules alone, the effect of a double dose of metoprolol Durules® (400 mg once daily) was compared with a fixed combination of 200 mg metoprolol and 25 mg hydrochlorothiazide (Selokomb®). The study followed a double-blind cross-over schedule in 2 parallel groups. The reduction in diastolic blood pressure (p〈0.01) was comparable in the two groups. A significant fall (p〈0.01) in systolic blood pressure occurred with the metoprolol/hydrochlorothiazide combination. The subsequent change from the double dose of metoprolol Durules to the combination therapy also resulted in a fall in systolic blood pressure (p〈0.05). Mean serum potassium and blood glucose levels did not change after each alteration in therapy. Most of the side-effects mentioned were mild and transient in character.
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  • 63
    Digitale Medien
    Digitale Medien
    Springer
    European journal of clinical pharmacology 17 (1980), S. 161-164 
    ISSN: 1432-1041
    Schlagwort(e): nifedipine ; hypertension ; blood pressure ; heart rate ; plasma renin activity ; aldosterone ; clinical trial
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary The magnitude and duration of the antihypertensive effect of nifedipine were studied in 7 cases of moderate essential hypertension. In a double-blind crossover study, nifedipine 10 mg or a placebo were administered sublingually 4 times a day for 2 days, and the results were compared. Each dose of nifedipine reduced systolic and diastolic blood pressure by 14% both in the supine and upright positions. The antihypertensive action lasted for about 3 h and it was not cumulative. The reduction in blood pressure was associated with a temporary increase in heart rate. Administration of nifedipine 10 mg did not significantly raise plasma renin activity or plasma aldosterone. The drug was well tolerated and no side effects were detected.
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  • 64
    Digitale Medien
    Digitale Medien
    Springer
    European journal of clinical pharmacology 17 (1980), S. 209-213 
    ISSN: 1432-1041
    Schlagwort(e): disopyramide ; bioavailability ; controlled-release tablets ; pharmacokinetics
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary Plasma concentrations and bioavailability of disopyramide following repeated administration of standard capsules and controlled-release tablets have been compared. Ten patients were randomized into two groups; Group I received disopyramide capsules 150 mg every 6 h for five days and subsequently disopyramide controlled-release tablets 300 mg every 12 h for further five days. Group II received the same preparations in the reverse order. There was a more rapid rise in disopyramide concentration after the capsules: the maximum of 10.7±0.6 µmol/l (mean ± SEM) was reached within 1.8±0.4 h as compared to 10.6±0.4 µmol/l within 4.0±0.3 h after the controlled-release tablets. No significant difference in the fluctuations in individual plasma concentrations during each dose interval at steady state were observed after ordinary capsules compared to controlled-release tablets. The extent of bioavailability was the same. Eight patients reported some side-effects during the capsule period and nine during the controlled-release tablet period.
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  • 65
    Digitale Medien
    Digitale Medien
    Springer
    European journal of clinical pharmacology 17 (1980), S. 215-221 
    ISSN: 1432-1041
    Schlagwort(e): L-dopa ; elderly ; pharmacokinetics ; bioavailability
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary Previous studies have suggested that the absorption of L-dopa in the elderly Parkinsonian patient might be unusually efficient. In the present investigation, the systemic availability of L-dopa was examined in 5 elderly Parkinsonian patients (mean age=77 years) and 6 young, healthy volunteers (mean age=26 years) following a single oral 300 mg dose of L-dopa. Quantitation of plasma levels of intact L-dopa was effected by ion-exchange column chromatography and spectrofluorimetry. The L-dopa plasma concentration-time profiles obtained confirmed the considerable intersubject variability in the absorption of L-dopa previously reported in the literature. Maximum plasma concentrations of L-dopa generally occurred within 60 min of administration of the dose. The existence of more than one plasma peak of L-dopa concentration was displayed in 45% of the subjects studied. This characteristic was not confined exclusively to either subject group. There was a significantly larger (P〈0.02) area under the plasma L-dopa concentration-time curve (AUC o ∞ ) in the elderly Parkinsonian patients (mean=234.69 µg · min/ml; SD=84.70) compared to the young, healthy volunteers (mean=82.33 µg · min/ml; SD=31.00). A significant (P〈0.01) correlation existed between AUC o ∞ and age (r=0.7970; n=11) among the subjects studied. The apparent elimination phase plasma half-life of L-dopa in the elderly Parkinsonian patients (mean=66.0 min; SD=11.1) was not significantly different to that observed in the young, healthy volunteers (mean=74.0 min; SD=18.1). These results suggest that there may be an age-related alteration to the disposition of orally administered L-dopa in the elderly Parkinsonian patient.
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  • 66
    Digitale Medien
    Digitale Medien
    Springer
    European journal of clinical pharmacology 17 (1980), S. 333-337 
    ISSN: 1432-1041
    Schlagwort(e): atenolol ; chlorthalidone ; hypertension ; chronic treatment ; co-administration ; plasma half-life ; urine half-life
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary The pharmacokinetics of atenolol with and without the co-administration of chlorthalidone were studied in five hypertensive subjects. Concomitant administration of chlorthalidone appears to have little if any effect on the pharmacokinetics of atenolol during treatment for 7 days. The atenolol elimination half-lives were 6.7±1.1 and 6.3±0.9 h, respectively, with and without chlorthalidone. Two healthy volunteers also received a single 50 mg oral dose of chlorthalidone. Their blood profiles and pharmacokinetics were similar to those observed in hypertensive subjects, but a statistically significant difference (p〈0.01) was found between the urinary excretion half-lives of chlorthalidone. This difference may be because chronic administration of the drug caused saturation of red cell binding.
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  • 67
    Digitale Medien
    Digitale Medien
    Springer
    European journal of clinical pharmacology 17 (1980), S. 385-391 
    ISSN: 1432-1041
    Schlagwort(e): sulpiride ; pharmacokinetics ; serum clearance ; renal clearance ; bioavailability ; healthy volunteers
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary The pharmacokinetics of sulpiride was studied in 6 healthy volunteers after intravenous and oral (tablets) administration of 100 mg. An open two- and in two subjects a three-compartment model was applied following intravenous administration. The average total distribution volume during the terminal slope was 2.72±0.66 l/kg and total systemic clearance was 415±84 ml/min. The serum half-life of the terminal slope following intravenous administration averaged 5.3 h (range 3.7–7.1 h) according to the two-compartment model. In two subjects the half-lives were 11.0 and 13.9 h when the three-compartment model was applied. Determination of urinary excretion rates of unchanged sulpiride indicated a half-life of 7.15 h. Following intravenous administration, 70±9% of the dose was recovered unchanged in urine within 36 h; the mean renal clearance was 310±91 ml/min. Sulpiride was absorbed slowly, with peak concentrations appearing between 3 and 6 h after oral administration. The recovery of unchanged drug in urine following oral administration was 15±5% of the dose, with a mean renal clearance of 223±47 ml/min. The bioavailability determined from combined plasma and urine data was only 27±9%. The low bioavailability was probably due to incomplete absorption.
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  • 68
    Digitale Medien
    Digitale Medien
    Springer
    European journal of clinical pharmacology 18 (1980), S. 43-50 
    ISSN: 1432-1041
    Schlagwort(e): enteral drug absorption ; development ; bioavailability ; neonates
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary There is little information about enteral drug absorption during development compared to that about drug distribution, metabolism and excretion. Therefore, the bioavailability, i.e. the amount and rate of absorption of various drugs (sulfonamides, phenobarbital, digoxin, β-methyldigoxin) and test substances (D(+)-xylose, L(+)-arabinose) was investigated in 580 children using pharmacokinetic methods. The amounts of the drugs absorbed, determined by Dost's law of corresponding areas, showed no age dependence. But the rate of absorption, ka, calculated from the concentration time curves using a digital approximation procedure (RIP), is low at the time of birth and reaches adult values after the neonatal period. This phenomenon is identical for all of the substances tested. A prolonged gastric emptying time in the neonate does not seem to be responsible for the delayed absorption since the lagtime is not related to age. Stimulation of intestinal motility with metoclopramide increases the absorption rates, both in neonates and older children, but the age dependent differences remain. Using various dosages of L(+)-arabinose the parameters of the saturation kinetics could be determined. In neonates Vmax values are significantly lower than in older children. Similarly, the affinity constant $$\mathop K\limits^ \star$$ indicates a decreased capacity of enteral absorption in neonates compared with older children. Bioavailability data from adults cannot be accepted without further investigation since the rate of enteral drug absorption depends on age.
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  • 69
    Digitale Medien
    Digitale Medien
    Springer
    European journal of clinical pharmacology 24 (1983), S. 21-30 
    ISSN: 1432-1041
    Schlagwort(e): clonidine ; bioavailability ; blood pressure ; elimination half-life ; pharmacokinetics ; plasma catecholamines ; rebound phenomenon
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary Using considerably improved analytical methods, the kinetics and effects of clonidine were observed in healthy volunteers over periods of time more than 3 times longer than those previously reported. The high sensitivity and small work load of the newly developed method permitted the performance of low-dose and multipledose trials. 1. The complete bioavailability of clonidine and its elimination half-life (20 to 25.5 h) remained constant after single and multiple doses. 2. Approximately 62% of a given dose was excreted unchanged in the urine, independent of the quantity administered (0.075, 0.15, 0.2, 0.25 or 0.3 mg), the drug formulation (solution, tablet, Perlonget) or of the mode of administration (i.v., p.o.; single or multiple doses). 3. As the pharmacokinetics of the drug were affected by entero-hepatic circulation, it cannot be described by a conventional, open one or two compartment model. 4. The time courses of the plasma clonidine concentration and its drug effects ran asynchronously. 5. On cessation of chronic clonidine administration, blood pressure and plasma catecholamine levels increased to pretreatment levels without exhibiting any “overshoot” reaction.
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  • 70
    ISSN: 1432-1041
    Schlagwort(e): theophylline ; smoking ; sustained release formulation ; dosage forms ; multidose pharmacokinetics ; bioavailability ; circadian variation in kinetics
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary The pharmacokinetics and bioavailability of theophylline following 10 days of multiple doses of a plain uncoated (640 mg, q.i.d.) and a sustained-release tablet formulation (600 mg, b.i.d.) were related to habitual smoking in 11 healthy adult male volunteers, who had previously taken part in a single-dose study of an intravenous preparation of theophylline and of the same oral dosage form. There were significant differences (p〈0.05 to 0.01) in the steady-state mean and minimum theophylline concentration and AUC between the groups (6 smokers versus 5 nonsmokers), but not between other variables. A difference (p〈0.05) in peak time was also found between the dosage forms. The mean elimination t1/2 was significantly (p〈0.05) shorter in smokers than in nonsmokers. The intersubject variability in plasma theophylline concentration observed on the final trial day in the smoking group was larger and diverged more from simulation curves generated from the mean pharmacokinetic parameters of the single-dose study of the same formulations as compared to that of the nonsmoking group. There was no significant difference between the two groups in the mean accumulation ratio and absolute bioavailability of the two dosage forms. The mean morning (7 a.m.) trough theophylline concentrations after both formulations were significantly (p〈0.05 to 0.01) greater than the evening (7 p.m.) values within the same group. The average number of reported side-effects was significantly (p〈0.001) greater during the earlier period (Days 1 to 3) than the later period of the trial. A trend was observed suggesting that the incidence of side-effects was less in smokers than in nonsmokers. The results indicate that smoking is a determinant not only of enhanced elimination of theophylline but that it also produces more variability in the plasma level, irrespective of the dosage form administered or the dosing scheme employed. There may be circadian variation in theophylline kinetics.
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  • 71
    Digitale Medien
    Digitale Medien
    Springer
    European journal of clinical pharmacology 24 (1983), S. 415-419 
    ISSN: 1432-1041
    Schlagwort(e): prednisolone ; bioavailability ; non-linear pharmacokinetics ; protein binding
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary The pharmacokinetics of prednisolone after oral and intravenous administration of 10 and 20 mg have been studied. Serum protein binding of prednisolone was also measured after the i.v. injections. The bioavailability after oral administration was 84.5% after 10 mg and 77.6% after 20 mg (p〉0.05). Dose dependent pharmacokinetics were found, the VDss and Clt being significantly larger (p〈0.01) after 20 mg i.v. than after 10 mg i.v. The protein binding of prednisolone in all subjects was non-linear, and is the most likely cause of the dose dependent pharmacokinetics, as there was no dose dependent variation in elimination half-time.
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  • 72
    ISSN: 1432-1041
    Schlagwort(e): ranitidine ; duodenal ulceration ; pharmacokinetics ; non-responders ; therapeutic response ; bioavailability
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary The pharmacokinetics of orally administered ranitidine were studied in 17 male patients with chronic duodenal ulceration. The patients were divided into 2 groups, 10 responders and 7 nonresponders, on the basis of their endoscopic response to ranitidine treatment. The 10 responders were studied both after a single 150 mg dose (SD) and after multiple dosing (MD) with ranitidine 150 mg twice daily for 4 weeks. The area under the curve (AUC) and maximum concentration (Cmax) were significantly higher (p〈0.01 andp〈0.05, respectively) after MD than after SD, but the half-life (t1/2) and minimum concentration (Cmin) 12 h postdosing did not differ. The non-responders were studied after MD only and their pharmacokinetic characteristics were compared with those of responders. No differences between the 2 groups were found. However, 2 non-responders had particularly low plasma ranitidine levels and high acid output. Such patients may need larger doses of ranitidine for adequate suppression of gastric acid. Five patients (4 responders and 1 non-responder) received ranitidine 20 mg i.v. The drug followed a two-compartment model, with mean values for t1/2β, volume of distribution steady-state and total plasma clearance of 80 min, 701 and 680 ml/min, respectively. The oral bioavailability of ranitidine in these 5 patients showed wide variation (27–76%; mean 51%).
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  • 73
    Digitale Medien
    Digitale Medien
    Springer
    European journal of clinical pharmacology 24 (1983), S. 573-577 
    ISSN: 1432-1041
    Schlagwort(e): beta-blockers ; serum lipoproteins ; atenolol ; metoprolol ; hypertension ; VLDL ; HDL ; hypertriglyceridaemia ; hypercholesterolaemia ; side effects
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary Several β-blockers increase VLDL-TG and decrease HDL-cholesterol concentrations. The underlying mechanism ist not yet clear. Some studies have suggested that the effect is less pronounced during treatment with selective β-blockers. The effects of 2 such drugs, metoprolol 200 mg/day and atenolol 50 mg/day, have been compared in 50 hypertensive patients (WHO Stage I–II), mean age 47 years. Serum lipoproteins were determined in 20 patients before treatment and after treatment with either drug for 3 months. Both drugs were equally effective in reducing blood pressure. After atenolol the initial VLDL-cholesterol concentration of 1.04 mmol/l had not changed, but it rose to 1.29 mmol/l after metoprolol (p〈0.05). The HDL-cholesterol concentration 1.42 mmol/l did not fall during atenolol treatment, but during metoprolol there was a small reduction to 1.31 mmol/l (p〈0.05). Hyperlipoproteinaemia is common in hypertensive patients, 40% of the present group had hypertriglyceridaemia and 25% had hypercholesterolaemia. Thus, atenolol 50 mg was found not to affect lipoproteins, whereas metoprolol 200 mg increased the VLDL concentration in 75% of the patients.
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  • 74
    Digitale Medien
    Digitale Medien
    Springer
    European journal of clinical pharmacology 24 (1983), S. 761-767 
    ISSN: 1432-1041
    Schlagwort(e): theophylline ; bioavailability ; sustained release tablet ; pharmacokinetics ; Theograd-250
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary The bioavailability of theophylline after oral administration of a new sustained release tablet Theograd®-250 mg was studied in 7 healthy volunteers, under fasting and non-fasting conditions. Whilst fasting the bioavailability was moderate at 64±22% (mean±SD), whereas in the non-fasting state the relatively high bioavailability of 90±13% was found. The drug appeared to be significantly more slowly absorbed when a tablet was taken after a meal, than when it was ingested on an empty stomach. In the former case, the peak level was reached after 6.9±1.0 h, whereas in the fasting state the maximum serum concentration occurred 4.0±1.7 h after administration of the drug. Despite the slow absorption, the peak non-fasting level of 4.4±1.4 mg·l−1 was significantly higher than the 3.1±1.0 mg·l−1 observed in the fasting state. The profiles of the serum concentration-time curves showed that the concentration remained above 75% of Cmax for 8.7±1.3 h in the fasting and 9.0±1.1 h in the non-fasting state. It was concluded that to define the optimal dosage regime for sustained release oral dosage forms of theophylline, the influence of food on absorption from these preparations should be taken into account. Based on the present results, Theograd®-250 mg tablets have predictable absorption and a high (90%) bioavailability if taken after a meal.
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  • 75
    Digitale Medien
    Digitale Medien
    Springer
    European journal of clinical pharmacology 25 (1983), S. 69-72 
    ISSN: 1432-1041
    Schlagwort(e): levodopa ; intestinal absorption ; small intestine ; bioavailability ; benserazide ; presystemic clearance
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary In four healthy subjects the intestinal absorption of levodopa (l-dopa) was investigated by measuring the plasma concentration of the amino acid following the administration of l-dopa at three different sites in the small intestine. In order to minimize presystemic clearance of l-dopa, the subjects were pretreated with the peripheral decarboxylase inhibitor benserazide 3×50 mg every 8 h on the previous day and 1×50 mg 2 h prior to administration of the l-dopa. L-dopa 100 mg dissolved in 0.05 N HCl and 50 mg benserazide dissolved in 0.05 N HCl were coadministered. Under these conditions no difference in tmax, cmax or AUC of l-dopa was observed between administration of the drug into the proximal or the distal part of duodenum, or into the upper part of jejunum. The results indicate that in healthy subjects, during inhibition of peripheral decarboxylase, the rate and extent of l-dopa absorption does not differ at any site in the upper small intestine.
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  • 76
    Digitale Medien
    Digitale Medien
    Springer
    European journal of clinical pharmacology 24 (1983), S. 49-53 
    ISSN: 1432-1041
    Schlagwort(e): felodipine ; hypertension ; cardiac failure ; haemodynamic effects ; non-invasive monitoring
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary The haemodynamic effects of a new vasodilating drug, felodipine, were studied in eight, healthy, male subjects, aged 22–31 years. The drug was given as an oral solution in the dose of 0.15 mg/kg. Thirty-five minutes later further dose of 0.15 mg/kg was administered. Felodipine induced a pronounced decrease in diastolic blood pressure (maximal effect 15±4 mm Hg) and in the systemic vascular resistance. Cardiac output increased (maximum by 4.2±0.3 l/min), due to an increase both in the stroke volume and the heart rate. The maximal increase in the stroke volume (measured from echo cardiograms) and the heart rate were 33±5 ml and 23±3 beats/min, respectively. Felodipine caused a significant decrease in the pre-ejection period (23±3 ms) and an increase in the left ventricular ejection time (29±3 ms). The quotient PEP/LVET fell from 0.36±0.01 to 0.28±0.01. Significant activity of felodipine could be recorded at a plasma level of about 15 nmol/l. When the maximal haemodynamic effects were recorded the plasma level was about 40 nmol/l. After a cumulative dose of 0.30 mg/kg, there was a twofold variation in the maximal plasma level (from 31 to 61 nmol/l). The results of the present investigation are in agreement with previous haemodynamic studies in animals. It would appear that felodipine is a potent arteriolar vasodilator and it might well be of considerable value in the management of patients with hypertension or congestive cardiac failure.
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  • 77
    Digitale Medien
    Digitale Medien
    Springer
    European journal of clinical pharmacology 24 (1983), S. 191-197 
    ISSN: 1432-1041
    Schlagwort(e): hypertension ; beta-blocker ; diuretic ; screening ; naturalistic
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie , Medizin
    Notizen: Summary A naturalistic study was set up to screen, identify and treat hypertensive patients aged 20–60 years in a rural general practice. 3,222 patients (92%) of a stable population of 3,489 were screened by 2 nurse research assistants and of these 455 patients (14%) were found to be hypertensive or borderline hypertensive. After careful assessment, 192 of these patients were found suitable for treatment and subsequently 138 entered the study. Two well recognised treatment regimes were used and no significant difference between patient response resulted. 84 patients (60.9%) completed the 2 year duration of the study discussed here. The cost of the study is not feasible in an average general practice, but day to day running of such a project, run along clearly defined treatment regimes was managed easily by 2 research assistants: this reduced, therefore, the work load on individual general practitoners.
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  • 78
    Digitale Medien
    Digitale Medien
    Springer
    Bulletin of experimental biology and medicine 95 (1983), S. 412-414 
    ISSN: 1573-8221
    Schlagwort(e): brain ; blood-brain barrier ; hypertension ; angiotensin ; noradrenalin
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Biologie , Medizin
    Materialart: Digitale Medien
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  • 79
    Digitale Medien
    Digitale Medien
    Springer
    Bulletin of experimental biology and medicine 96 (1983), S. 1631-1633 
    ISSN: 1573-8221
    Schlagwort(e): smooth muscles ; calcium ; intracellular vesicles ; hypertension
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Biologie , Medizin
    Materialart: Digitale Medien
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  • 80
    Digitale Medien
    Digitale Medien
    Springer
    Bulletin of experimental biology and medicine 90 (1980), S. 1082-1085 
    ISSN: 1573-8221
    Schlagwort(e): hypertension ; adrenalectomy ; fat cells ; isoproterenol
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Biologie , Medizin
    Materialart: Digitale Medien
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  • 81
    Digitale Medien
    Digitale Medien
    Springer
    Journal of pharmacokinetics and pharmacodynamics 11 (1983), S. 561-576 
    ISSN: 1573-8744
    Schlagwort(e): methylprednisolone ; bioavailability ; pharmacokinetics ; oral and parenteral administration
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie
    Notizen: Abstract This study was conducted to evaluate the influence of route of administration upon the bioavailability and pharmacokinetics of methylprednisolone sodium succinate. Fourteen healthy adult male volunteers received 40 mg doses of methylprednisolone as the following treatments after an overnight fast in a 4-way crossover design: (a) as a 1 ml i.v. bolus;(b) as a 1 ml i.m. injection;(c) administered as an oral solution;and (d) as 5×8 mg oral tablets. Both the ester and free methylprednisolone were determined in plasma and urine. Study results indicate that the ester is rapidly and extensively converted to free methylprednisolone after all routes. The extent of methylprednisolone absorption was equivalent after i.v. and i.m. administration. Both orally administered treatments resulted in a lower extent of absorption attributed to a first-pass effect. Although a slightly lower extent of absorption was demonstrated following the oral administration of the methylprednisolone sodium succinate solution relative to the methylprednisolone oral tablets, this average difference of 9% would probably be of minimal therapeutic importance.
    Materialart: Digitale Medien
    Standort Signatur Erwartet Verfügbarkeit
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  • 82
    Digitale Medien
    Digitale Medien
    Springer
    Journal of pharmacokinetics and pharmacodynamics 8 (1980), S. 463-481 
    ISSN: 1573-8744
    Schlagwort(e): bioavailability ; absorption ; deconvolution ; computer program for deconvolution ; algorithm for deconvolution ; drug input evaluation ; input response in linear pharmacokinetic systems ; pentobarbital absorption ; cimetidine absorption
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie
    Notizen: Abstract The procedure of deconvolution to evaluate the rate and the extent of input from absorption data and data from intravenous administration is the most fundamental and least assumptive method of accurately evaluating drug absorption in linear pharmacokinetics. It is shown for linear systems that if the absorption response and the response from an intravenous infusion or bolus administration are both well approximated by a polyexponential function, then the rate of absorption can be expressed as a sum of exponentials. An algorithm and computer program are presented whereby the absorption function is uniquely defined from the model-independent parameters of the polyexponential expressions fitted to the absorption data and data from intravenous administration. Fitting a sum of exponentials to data has become a routine procedure in pharmacokinetics. The method presented therefore makes the previously complex task of deconvolution a simple procedure. The deconvolution approach is discussed in relation to conventional methods of evaluating drug absorption and appears to have some distinct advantages over these methods. The method is tested using simulated data and demonstrated using pentobarbital and cimetidine data from human subjects.
    Materialart: Digitale Medien
    Standort Signatur Erwartet Verfügbarkeit
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  • 83
    Digitale Medien
    Digitale Medien
    Springer
    Journal of pharmacokinetics and pharmacodynamics 8 (1980), S. 243-255 
    ISSN: 1573-8744
    Schlagwort(e): quinidine ; bioavailability ; absorption ; solutions ; rapidiy releasing tablets ; humans
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie
    Notizen: Abstract The gastrointestinal absorption of quinidine from three commercially available tablet products has been compared to that from a quinidine sulfate solution previously found to have 70% of the systematic availability of an intravenous dose. Quinidine gluconate solution was included in the study to compare the absorption characteristics of the two quinidine salts. The tablets were given in a counterbalanced sequence preceded by one quinidine solution and followed by the other in a crossover design. The three tablets proved to be equivalent to one another with respect to extent and rate of absorption. The absorption properties of the two solutions were indistinguishable. The tablets were equivalent to the solutions in extent but not in rate of absorption.
    Materialart: Digitale Medien
    Standort Signatur Erwartet Verfügbarkeit
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  • 84
    ISSN: 1573-8744
    Schlagwort(e): theophylline ; absorption ; bioavailability ; enteric release ; tablets ; plasma concentrations ; dissolution data
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie
    Notizen: Abstract In a single-dose bioavailability study, Wales, Robinson, Columbia, and Choledyl (Warner/Chilcott) enteric-coated tablets all allowed a bioavailability of theophylline (99%±25%, 102%±23%,103%±18%, and 98%±15%;mean±SD, n=12) statistically indistinguishable from that of the standard uncoated tablet (Searle 200 mg aminophylline). Only the Wales and Choledyl tablets (7.6, 4.2 hr) could be shown (p〈0.05) to generate a peak plasma theophylline concentration later than the standard (1.4 hr). All tablet brands demonstrated a significant lag time before appearance of theophylline in the plasma, and both Wales and Choledyl tablets also had a (t peak -t tag )statistically different from that of the standard. Despite misleading indications from the mean plasma profile (plasma concentrations at each sampling time averaged over all subjects), plasma data from the individual participants and in vitrodissolution data show that, while release of theophylline from the Wales tablet might be inordinately slow, this is not a sustained-release preparation. Of the enteric-coated tablets only the Columbia product allowed significant levels in the first sample after dosage. Five of the 18 Columbia doses gave rise to 40–99%of the peak concentration in the 1- hr sample. In vitro,it takes 39±14 min for 40% of the theophylline content of Columbia tablets to dissolve in simulated intestinal fluid. Surprisingly rapid delivery of an entericcoated tablet to the duodenum would appear to be required to allow a significant percentage of theophylline to be dissolved and absorbed before 1 hr. None of 12 Columbia tablets tested in vitro,however, allowed dissolution of more than 0.2% of their theophylline content during 1 hr immersion in simulated gastric fluid. Since once in intestinal fluid Columbia tablets appear to dissolve more rapidly than the other enteric products, it is not clear whether the five Columbia tablets in question had imperfections or whether, in fact, this tablet brand more closely than the others represents the ideal of immediate release once in the duodenum. Plasma samples should be taken as early as 15 min after dosage when evaluating the bioavailability of enteric release products.
    Materialart: Digitale Medien
    Standort Signatur Erwartet Verfügbarkeit
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  • 85
    Digitale Medien
    Digitale Medien
    Springer
    Journal of pharmacokinetics and pharmacodynamics 8 (1980), S. 347-362 
    ISSN: 1573-8744
    Schlagwort(e): griseofulvin ; bioavailability ; HPLC assay ; plasma levels ; human study
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie
    Notizen: Abstract The relative bioavailability of ten marketed dosage forms of griseofulvin was evaluated in two separate crossover studies. Each study utilized 12 healthy subjects, with eight of the subjects being common to both studies. Plasma griseofulvin concentrations were determined 1, 2, 3, 4, 6, 8, 10, 25, 34, 49, and 73 hr after dosing, using a high-pressure liquid chromatographic method. The “high-dose” study compared four microsize dosage forms administered as 500-mg doses and two ultramicrosize formulations given as 250-mg doses. The “low-dose” study employed four 250-mg microsize products and two 125-mg ultramicrosize products. The individual plasma level-time profiles for the majority of doses suggested prolonged absorption of microsize griseofulvin. The ultramicrosize dosage forms exhibited peak concentrations which were not significantly different (p〉0.05) from those of the microsize products administered as twice the dose. In the high-dose study, the two 250-mg ultramicrosize dosage forms exhibited areas under the plasma level-time curve (AUC) which were significantly (p〈0.05) less than the AUCs for all but one of the 500-mg microsize products. In the low-dose study the AUCs for the ultramicrosize products were significantly lower than the AUCs for all of the microsize dosage forms. Significant differences were also noted among the AUCs for the microsize products, although the maximum difference was less than 20% in both studies. A comparison of the AUCs observed in the high- and low-dose studies revealed that the AUCs for two of the 500-mg microsize dosage forms were only approximately 75% the AUC predicted from the 250-mg dose for the eight subjects common to both studies. All other formulations exhibited a dose proportionality for AUC.
    Materialart: Digitale Medien
    Standort Signatur Erwartet Verfügbarkeit
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  • 86
    ISSN: 1573-8744
    Schlagwort(e): theophylline ; absorption ; bioavailability ; sustained release ; tablets ; plasma concentrations ; mean plasma concentrations ; steady-state projections
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie
    Notizen: Abstract Absorption of theophylline from three commercial products labeled as sustained release was compared to the absorption from a standard uncoated tablet (Searle 200-mg aminophylline tablet) in a single-dose study. Aminodur tablets (Cooper) and Slophyllin Gyrocap capsules (Dooner) had bioavailability (100.2%±19.8% and 98.5%±13.8%) statistically indistinguishable from that of the standard but showed significantly slower absorption (peak times of 10,4±2.8 and 4.36±1.35 hr) and lower peak plasma concentrations (13.9±4.5 and 22.6±3.5gmg/ml/g dose) than the standard (t peak ,1.52±0.45 hr; Cpeak,28.l±6.2μg/ml/g dose). The time of the plasma concentration peak (2.47±1.38 hr) after a dose of Tedral S.A. (Warner/Chilcott) was not statistically different from that after the standard, but both the peak concentration (16.0±3.9 gmg/ml/g dose) and bioavailability (76.0±18.4%) were. Multiple-dose projections from single-dose data indicate that of the three test products only Aminodur maintains reasonably constant interdose plasma levels during 12 hourly dosing. With an 8 hourly dosing schedule Gyrocaps also might be satisfactory. Reasonable predictions of the plasma concentrations arising from Aminodur doses have been made using a single-compartment body model and assuming input from an outer followed by an inner layer of the tablet. Typically a single dose of a preparation designed for constant release of drug over 12 hr should not produce a plasma concentration plateau in subjects with an average 6.1-hr drug half-life. The apparent plateau in the mean plasma profile (i.e., concentrations at each sampling time averaged over all subjects) for Aminodur doses is evaluated. The interpretation commonly being implied in the publication of mean profiles from bioavailability studies is misleading, particularly when applied to sustained-release preparations.
    Materialart: Digitale Medien
    Standort Signatur Erwartet Verfügbarkeit
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  • 87
    Digitale Medien
    Digitale Medien
    Springer
    Journal of pharmacokinetics and pharmacodynamics 11 (1983), S. 205-214 
    ISSN: 1573-8744
    Schlagwort(e): bioavailability ; clearance ; V area ; V ss
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie
    Notizen: Abstract The limitations of using estimates of extent of bioavailability (F) based on the assumption that either clearance (CL) or Varea remain, constant are discussed in relation to the situation where CL changes between doses. When estimates of F assume CL to remain constant, the entent of the error is the same for all drugs where the percentage change in CL is the same. Assuming Varea to remain constant, the error in F will vary between drugs for similar percentage changes in CL and is related to the extent to which the kinetics of the disposition process deviate from a one compartment body model. A noncompartmental method is described where, provided the reference dose is given intravenously, F can be estimated based on the assumption that Vss remains constant between doses. This method is more accurate than those based on the assumption that either CL or Varea remain, constant when CL changes between doses, but is subject to error when the terminal loglinear slope of Cp vs. time better reflects the process of absorption rather than elimination.
    Materialart: Digitale Medien
    Standort Signatur Erwartet Verfügbarkeit
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  • 88
    Digitale Medien
    Digitale Medien
    Springer
    Journal of pharmacokinetics and pharmacodynamics 11 (1983), S. 529-545 
    ISSN: 1573-8744
    Schlagwort(e): bioavailability ; nitrofurantoin ; capacity-limited elimination
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Chemie und Pharmazie
    Notizen: Abstract The influence of route of administration on the absolute bioavailability and GI tract absorption of nitrofurantoin was investigated in rabbits. The disposition of nitrofurantoin was described by a one-compartment model with simultaneous first-order and Michaelis-Menten type elimination kinetics, and bioavailability was estimated by nonlinear assessment. The plasma levels following oral administration were significantly lower than those after intravenous administration, and absolute Fvalues for oral administration were approximately 0.3. However, Fvalues following intraduodenal administration and portal vein infusion were nearly unity, and it was concluded that the reduction of bioavailability following oral administration could not be attributed to metabolism by intestinal microflora or to the hepatic first-pass effect. Thus, reduction of Fvalues following oral administration is probably due to gastric degradation of the drug. The effects of factors influencing bioavailability, such as water volume taken with the drug, change of gastric emptying rate and effect of particle size, were also investigated. Increase of volume of water administered tended to improve the bioavailability, and a particle size dependency was also observed.
    Materialart: Digitale Medien
    Standort Signatur Erwartet Verfügbarkeit
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  • 89
    Digitale Medien
    Digitale Medien
    Springer
    Bulletin of experimental biology and medicine 90 (1980), S. 1510-1513 
    ISSN: 1573-8221
    Schlagwort(e): adaptation ; hemorrhage ; hypotension ; hypertension ; reinfusion
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Biologie , Medizin
    Materialart: Digitale Medien
    Standort Signatur Erwartet Verfügbarkeit
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