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  • pharmacokinetics  (23)
  • Drosophila melanogaster  (5)
  • Springer  (28)
  • American Physical Society
  • BioMed Central
  • Springer Nature
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  • 1
    Electronic Resource
    Electronic Resource
    A double-blind and cross-over comparison of once daily doxazosin and placebo with steady-state pharmacokinetics in elderly hypertensive patients (1988)
    Springer
    European journal of clinical pharmacology 34 (1988), S. 119-123 
    Details
    ISSN: 1432-1041
    Keywords: doxazosin ; hypertension ; alpha1-adrenoceptor inhibitor ; elderly patients ; pharmacokinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The α1-adrenoceptor antagonist doxazosin has been compared with placebo in 40 elderly hypertensive patients (mean age 71.4 years). At the end of 10 weeks once daily treatment with doxazosin the mean 24-h post-dose changes in standing and supine blood pressure compared with placebo were −6.9/−5.6 mmHg (systolic/diastolic) and −6.2/−5.5 mmHg respectively. The reductions in standing and supine diastolic blood pressures were statistically significant compared with placebo. At the end of treatment steady-state pharmacokinetics were evaluated in 18 patients. The plasma elimination half-life during the dose interval in these patients was 16.1 h (range 10.1–27.1 h) and the median time to peak plasma concentration was 3 h (range 1–4 h). One patient was withdrawn because of adverse effects (headache, weakness, and sweating) during doxazosin treatment. Once daily doxazosin reduced diastolic blood pressure and was well tolerated in these elderly hypertensive patients.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00614546
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  • 2
    Electronic Resource
    Electronic Resource
    Pharmacokinetics of zimelidine (1980)
    Springer
    European journal of clinical pharmacology 17 (1980), S. 111-116 
    Details
    ISSN: 1432-1041
    Keywords: zimelidine ; norzimelidine ; antidepressants ; pharmacokinetics ; bioavailability
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: 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.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00562618
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  • 3
    Electronic Resource
    Electronic Resource
    Development of behavioral competence in youngDrosophila melanogaster adults (1989)
    Springer
    Journal of insect behavior 2 (1989), S. 575-588 
    Details
    ISSN: 1572-8889
    Keywords: aging ; behavior ; central nervous system ; Drosophila melanogaster ; Diptera
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology
    Notes: Abstract We have monitored the ontogeny of several behaviors performed by young Drosophila melanogasteradults. Very young flies are less active than older flies and are less responsive to gravity, light, an odorant, and sucrose applied to their tarsi. In addition, very young males do not consume sucrose or perform any courtship behaviors in response to virgin females, which provide chemical and visual stimuli to courting males. The rate at which flies become maximally competent to respond to stimuli is a function of the behavior. Sensory and motor deficits are not solely responsible for young flies' inability to respond to the stimuli, which suggests that the central nervous system continues to develop after eclosion.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF01053355
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  • 4
    Electronic Resource
    Electronic Resource
    The effects of posture on the pharmacokinetics of intramuscular benzylpenicillin (1988)
    Springer
    European journal of clinical pharmacology 33 (1988), S. 629-635 
    Details
    ISSN: 1432-1041
    Keywords: benzylpenicillin ; posture ; intramuscular administration ; pharmacokinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Previous reports have produced conflicting results as to whether changes in posture affected the pharmacokinetics of the penicillins. We have studied the pharmacokinetics of intramuscularly administered benzylpenicillin in normal subjects during bedrest and ambulation and compared it with data obtained following intravenous administration of the same dose to the same subjects under the same conditions. The values of area under the curve, total clearance, mean residence time and renal clearance found during ambulation were 1175 (min·min·l−1), 488 (ml·min−1), 101 (min), and 264 (ml·min−1) (means). The corresponding values for bedrest were 1032 (min·mg·l−1), 544 (ml·min−1), 96.7 (min), and 315 (ml·min−1). There was a significant difference between the areas under the curve with change of posture but not between any of the other pharmacokinetic variables. The differences observed in this study are unlikely to be of clinical relevance. We suggest that the differences between the results of this study and those of previous studies may be related to the level of exercise undertaken by the subjects in the various studies.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00542500
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  • 5
    Electronic Resource
    Electronic Resource
    Interaction of metoprolol with lorazepam and bromazepam (1991)
    Springer
    European journal of clinical pharmacology 40 (1991), S. 405-409 
    Details
    ISSN: 1432-1041
    Keywords: Metoprolol ; lorazepam ; bromazepam ; interaction ; psychomotor tests ; pharmacokinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The interaction between metoprolol and bromazepam and lorazepam was studied in 12 healthy male volunteers aged 21–37 years. Metoprolol had no significant effect on the pharmacokinetics of bromazepam or lorazepam. However, bromazepam AUC was 35% higher in the presence of metoprolol. Bromazepam enhanced the effect of metoprolol on systolic blood pressure but not on diastolic blood pressure or pulse rate. Lorazepam had no effect on either blood pressure or pulse. Metoprolol did not enhance the effect of bromazepam on the psychomotor tests used in this study. Metoprolol caused a small increase in critical flicker fusion threshold with lorazepam but had no effect on the other tests. Lorazepam (2 mg) was more potent than bromazepam (6 mg) in the doses used in this study. The interaction of metoprolol with bromazepam and lorazepam is unlikely to be of clinical significance. No change in dose is necessary when using these drugs together.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00265852
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  • 6
    Electronic Resource
    Electronic Resource
    Pharmacokinetic-pharmacodynamic (PK-PD) modeling for a new antihypertensive agent (neutral metalloendopeptidase inhibitor SCH 42354) in patients with mild to moderate hypertension (1995)
    Springer
    European journal of clinical pharmacology 48 (1995), S. 351-359 
    Details
    ISSN: 1432-1041
    Keywords: Atrial natriuretic peptide ; Hypertension ; SCH 42354 ; blood pressure ; neutral metalloendopeptidase ; pharmacodynamics ; pharmacokinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Abstract SCH 42354, a neutral metalloendopeptidase (NEP) inhibitor, is the pharmacologically active form of the prodrug SCH 42495. It exerts antihypertensive effects by potentiating atrial natriuretic peptide (ANP) activity through inhibition of its hydrolysis by NEP. The objective of this study was to characterize the pharmacokinetics (PK) and pharmacodynamics (PD) of SCH 42354 in hypertensive males. SCH 42495 12.5 to 400 mg was administered orally to hypertensive men twice daily in a double-blind, placebo controlled multiple-dose parallel group design. Plasma SCH 42354 concentration and diastolic blood pressure (DBP) data were used to develop a PK-PD model using two approaches. In the first (non-integrated) approach, the “link” model was used to predict effect-site concentrations, and was applied to data obtained at the 300 and 400 mg BID doses only; data at the other (lower) doses were not amenable to modeling because of high variability. Effect-site concentration and DBP data were then fit to a sigmoid Emax PD model. For the 300 mg BID dose, PD parameters were: maximum effect (Emax), 8.1mmHg; no-drug effect (Eo), 3.6 mmHg; concentration corresponding to 50% of maximum response (EC50), 0.87 μg·ml−1; and gamma, 3.9. In the second (time-integrated) approach, plasma SCH 42354 concentration and effect data obtained over the entire dose range were integrated with respect to time. Average plasma concentration and DBP data were then fit to a simple Emax PD model. PD parameters obtained over the dose range were: Emax, 10.3 mmHg; Eo, 2.0 mmHg; and EC50, 0.7 μg·ml−1. These were similar to the estimates obtained from the first approach, demonstrating that the integrated (average) data allow PK-PD modeling over the (entire) dose range. The analysis showed that, at steady-state, a 400 mg BID dose of SCH 42495 produced an approximate 10 mmHg decrease in DBP in hypertensive males; the average plasma SCH 42354 concentration attained at this dose was approximately 1.8 μg·ml−1.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00194950
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  • 7
    Electronic Resource
    Electronic Resource
    The effect of pH on the buccal and sublingual absorption of captopril (1995)
    Springer
    European journal of clinical pharmacology 48 (1995), S. 373-379 
    Details
    ISSN: 1432-1041
    Keywords: Captopril ; sublingual ; pharmacokinetics ; pharmacodynamics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Abstract The effect of pH on the buccal and sublingual absorption of captopril was evaluated using in vitro techniques and human studies. Partitioning of captopril into n-octanol was lowest over the pH range 5 to 8 and highest at pH values 3, 4 and 9. Using the buccal absorption technique, the partitioning of captopril (2 mg) was examined in six healthy male volunteers from buffered solutions (pH 3, 4, 5, 6, 7, 8, and 9). Lowest buccal partitioning occurred at pH 3 while maximal buccal partitioning occurred at pH 7. These data clearly indicated that the buccal absorption of captopril did not obey the classical pH/partition hypothesis suggesting that mechanisms other than passive diffusion were involved in its absorption. Captopril pharmacokinetic and pharmacodynamic parameters were determined after administration of buffered sublingual captopril (pH 7, optimal pH for absorption as determined from the buccal partitioning data) and unbuffered sublingual captopril. The study was performed in eight healthy volunteers in a randomised single-blind cross-over fashion. The tmax for captopril was found to be approximately 11 minutes earlier after buffered versus unbuffered sublingual administration and AUC0–30 min increased by approximately 30% in the case of buffered captopril. Cpmax, AUC0–180 min and relative bioavailability did not differ between the buffered and unbuffered administration. Pharmacodynamic parameters (BP, heart rate and plasma renin activity) did not differ significantly between buffered and unbuffered sublingual administration. The increased rate of captopril absorption after buffered sublingual administration was small and is likely to offer little therapeutic advantage over conventional sublingual formulation.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00194953
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  • 8
    Electronic Resource
    Electronic Resource
    The effect of posture on the pharmacokinetics of intravenous benzylpenicillin (1986)
    Springer
    European journal of clinical pharmacology 30 (1986), S. 731-734 
    Details
    ISSN: 1432-1041
    Keywords: benzylpenicillin ; intravenous administration ; pharmacokinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary We have studied the pharmacokinetics of intravenously administered benzylpenicillin in normal subjects during bedrest and during ambulation. The values of total body clearance, mean residence time, and renal clearance found during ambulation were 487.4±100.5 ml/min, 36.23±13.45 min, and 309.4±93.4 ml/min (means ± SD). The corresponding values for bedrest were 543.6±122.6 ml/min, 35.27±10.21 min, and 324.1±145.3 ml/min. There were no significant differences between any of these pharmacokinetic variables with the change in posture. These results differ from previously reported results for the effects of posture on the pharmacokinetics of penicillins administered by extravascular routes, and suggest that the absorption of benzylpenicillin may be dependent on posture.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00608225
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  • 9
    Electronic Resource
    Electronic Resource
    Haemodynamic and pharmacokinetic evaluation of alfuzosin in man. A dose ranging study and comparison with prazosin (1989)
    Springer
    European journal of clinical pharmacology 37 (1989), S. 53-58 
    Details
    ISSN: 1432-1041
    Keywords: alfuzosin ; prazosin ; alpha1-adrenoceptor antagonist ; noradrenaline ; pharmacokinetics ; pharmacodynamics ; healthy volunteers
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary In an open dose ranging study with random inclusion of placebo, alfuzosin (α1-adrenoceptor antagonist) 1, 2.5 and 5 mg was administered to 6 healthy volunteers, 3 of the volunteers received 10 mg alfuzosin. Supine systolic blood (SBP) pressure was not reduced by alfuzosin although significant increases occurred in supine heart rate (HR) after 2.5 and 5 mg. In the standing position, SBP was reduced at 2 and 4 h with 5 mg alfuzosin; significant increases in HR occurred following 1, 2.5 and 5 mg at 2, 4, 6 and 8 h after administration. Exercise SBP was not reduced; diastolic blood pressure was significantly reduced at 4 and 6 h with 5 mg alfuzosin. More marked effects were seen in the 3 subjects who received 10 mg alfuzosin. After 1 and 5 mg, tmax ranged from 1–2 h; Cmax (4.1 to 20.8 ng · ml−1; AUC (0–24) 20 to 132 ng · ml−1 · h (1 and 5 mg respectively) increased progressively with dose indicating dose dependent kinetics; no significant changes occurred in the visual analogue scale for sedation. A comparison of alfuzosin 5 mg, prazosin 1 mg and placebo each administered for 4 days, indicated that alfuzosin did not significantly reduce standing SBP on either Day 1 or Day 4; prazosin reduced SBP at 2 and 4 h on Day 1 and 6 h on Day 4 compared to placebo. Standing HR was increased by alfuzosin at 2 h on Day 1 and Day 4; increases occurred with prazosin at 2, 4, 6 and 8 h on Day 1 and 6 h on Day 4. Supine plasma noradrenaline increased with alfuzosin and prazosin at 2 and 4 h on Days 1 and 4; the increases were not significantly different. The plasma elimination half-life (t1/2) for alfuzosin was 3.4 h and 3.1 h after acute and chronic administration; (t1/2) for prazosin was 2.6 and 2.9 h. In conclusion alfuzosin causes small reductions in systolic blood pressure, accompanied by a dose dependent increase in heart rate in the supine and standing position and following exercise.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00609425
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  • 10
    Electronic Resource
    Electronic Resource
    Sublingual captopril — a pharmacokinetic and pharmacodynamic evaluation (1991)
    Springer
    European journal of clinical pharmacology 40 (1991), S. 393-398 
    Details
    ISSN: 1432-1041
    Keywords: Captopril ; sublingual ; pharmacokinetics ; pharmacodynamics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary In this study we compared the pharmacokinetics and pharmacodynamics of captopril after sublingual and peroral administration. Single 25 mg doses of captopril were administered sublingually and perorally on two different occasions in a randomised cross-over fashion to eight healthy volunteers aged 22–35 years. The kinetics of unchanged captopril, plasma renin activity (PRA), BP and heart rate were studied over three hours after both peroral and sublingual administration of captopril. Mean pharmacokinetic parameters for unchanged captopril after sublingual administration were: Cmax, 234 ng·ml−1; tmax, 45 min; AUC (0–3 h), 15.1 μg·ml−1. min. Mean pharmacokinetic parameters for unchanged captopril after peroral administration were: Cmax, 228 ng·ml−1; tmax, 75 min; AUC (0–3 h), 17.0 μg·ml−1. min. tmax was significantly shorter when captopril was administered sublingually; all other pharmacokinetic parameters were equivalent. The plasma captopril concentrations achieved post drug administration led to increases in PRA and reductions in BP. tmax for PRA was 86 min for sublingual captopril and 113 min for perorally administered drug. Peak PRA values were, however, not significantly different. BP, as expected, was not reduced dramatically in these healthy volunteer subjects, however, in systolic BP vs time profiles, BP was significantly lower after volunteers received sublingual captopril. Heart rate increased slightly after captopril administration; there were no differences between the two routes of administration. Administration of captopril sublingually, therefore led to a more rapid attainment of plasma captopril concentrations and had a more rapid onset of pharmacological effect when compared with peroral administration.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00265850
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