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  • pharmacokinetics  (260)
  • Immunohistochemistry  (64)
  • Springer  (324)
  • American Meteorological Society
  • Blackwell Publishing Ltd
  • Cambridge University Press
  • International Union of Crystallography
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  • 1985-1989  (324)
  • 1975-1979
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  • 1960-1964
  • 1950-1954
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  • 11
    Electronic Resource
    Electronic Resource
    The disposition of biphenylacetic acid following topical application (1988)
    Springer
    European journal of clinical pharmacology 33 (1988), S. 639-642 
    Details
    ISSN: 1432-1041
    Keywords: biphenylacetic acid ; plasma and synovial fluid concentrations ; pharmacokinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Plasma and synovial fluid concentrations of biphenylacetic acid were determined following application of 3 g of 3% biphenylacetic acid gel to one knee of patients suffering from rheumatoid arthritis. The mean peak plasma concentration was 34 ng/ml. Synovial fluid concentrations tended to follow plasma concentrations but at a somewhat lower level, the mean peak synovial fluid concentration was 21 ng/ml. The average ratio of synovial fluid AUC (0–24 h) to plasma AUC (0–24 h) was 0.58, r=0.97. Where patients had bilateral effusions, the concentration in the ipsilateral knee at each time point examined was not significantly different to that in the contralateral knee, suggesting that absorption was initially into the plasma and subsequently into the synovium.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00542502
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  • 12
    Electronic Resource
    Electronic Resource
    Pharmacokinetic and pharmacodynamic properties of a new controlled-release formulation of metoprolol: A comparison with conventional tablets (1988)
    Springer
    European journal of clinical pharmacology 33 (1988), S. S9 
    Details
    ISSN: 1432-1041
    Keywords: metoprolol ; controlled-release formulation ; pharmacokinetics ; pharmacodynamics ; exercise heart rate ; healthy volunteers ; efficacy
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The pharmacokinetic and pharmacodynamic properties of a new multiple-unit, controlled-release (CR) formulation of metoprolol1 (metoprolol succinate, 95 mg once daily), which has almost constant (zero-order) release properties over most of a 24-h dose interval, have been compared with those of conventional metoprolol tablets (metoprolol tartrate, 100 mg once daily and 50 mg twice daily), in 12 healthy male volunteers. The steady-state plasma concentrations of metoprolol after five days of treatment varied less throughout the day with the CR than with the conventional formulation. This was associated with a considerably lower peak plasma concentration and the achievement of a significantly higher plasma concentration at the end of the dose interval. Similarly, the effect on exercise-induced tachycardia was maintained at a relatively constant level throughout the day after treatment with the CR formulation. A significantly greater effect 24 h after administration was achieved with the CR formulation, when compared with once-daily dosing with metoprolol tablets, 100 mg. Twice-daily dosing with metoprolol tablets, 50 mg, produced a similar β1-blocking effect at the end of the dose interval to that observed with metoprolol CR. Although the steady-state plasma concentrations indicated significantly lower systemic availability for the CR formulation, compared with both regimens of metoprolol tablets, the total effect over the dose interval, expressed as the area under the efficacy curve (AUEC), was similar for the three treatments. The relationship between steady-state plasma concentrations and the pharmacodynamic efficacy at corresponding times, indicated that plasma concentrations were more effectively utilized after the administration of the CR formulation than after the conventional tablet regimens. The results of this study clearly indicate the potential benefits offered by the new metoprolol CR formulation, under all circumstances where a constant degree of β1-selective blockade, without plasma peaks and troughs, is preferred.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00578406
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  • 13
    Electronic Resource
    Electronic Resource
    Influence of once-monthly rifampicin and daily clofazimine on the pharmacokinetics of dapsone in leprosy patients in Nigeria (1988)
    Springer
    European journal of clinical pharmacology 34 (1988), S. 73-76 
    Details
    ISSN: 1432-1041
    Keywords: dapsone ; rifampicin ; clofazimine ; leprosy ; drug interaction ; multidrug therapy ; pharmacokinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary In leprosy patients in Nigeria the influence of daily clofazimine and of once-monthly rifampicin on the pharmacokinetics of dapsone has been investigated. Three days after rifampicin the elimination half-life of dapsone was reduced from 40.4 to 25.3 h (n=23). Correspondingly, the plasma dapsone 24 h after the last dose had fallen significantly from 2.63 to 2.02 mg/l. Clofazimine did not cause change in the pharmacokinetics of dapsone. It was concluded that, although rifamipicin had a considerable influence on the pharmacokinetics of dapsone, there is no reason to adjust the dose of dapsone during multidrug therapy of leprosy.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF01061421
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  • 14
    Electronic Resource
    Electronic Resource
    Influence of digestive secretions and food on intestinal absorption of nicardipine (1988)
    Springer
    European journal of clinical pharmacology 34 (1988), S. 165-171 
    Details
    ISSN: 1432-1041
    Keywords: nicardipine ; pharmacokinetics ; gastrointestinal absorption ; influence of food ; intestinal perfusion
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The role of digestive absorption in the pharmacokinetics of nicardipine has been studied by the perfusion technique. Nicardipine (40 mg) was perfused in six healthy subjects at 5 ml/min for 2 h either in isotonic saline with (Experiment A) or without (B) an occlusive balloon isolating the test segment from digestive secretions, or in a nutrient solution (Experiment C). In Experiments A and B, 100% of nicardipine was absorbed from the jejunal lumen in a 25 cm test segment and in Experiment C it was slightly lower (94%). There was no relationship between the absorption of nicardipine and water movement or bile salt concentration in the jejunum. Nicardipine was already present in the first plasma sample taken after 15 min and the peak level was found at the end of the perfusion. The areas under the curves differed widely between subjects, because of interindividual variation in the first pass effect, but they were similar in Experiments A, B and C. The experimental data showed a good fit to a mode involving a two-phase absorption process. The first phase was associated with intestinal perfusion (zero order process) and the second with passage accross the intestinal wall (1st order process). In three further healthy subjects, nicardipine in saline was perfused in the jejunum and then in the ileum on consecutive days. Mean plasma levels over time were similar. The study showed that absorption of nicardipine both from the jejunum and the ileum was complete and was especially rapid. The food-induced change in the kinetics of absorption from the jejunum was too small to affect the pharmacokinetic parameters of nicardipine.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00614554
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  • 15
    Electronic Resource
    Electronic Resource
    Pharmacokinetics of nisoldipine in renal dysfunction (1988)
    Springer
    European journal of clinical pharmacology 34 (1988), S. 207-209 
    Details
    ISSN: 1432-1041
    Keywords: nisoldipine ; renal dysfunction ; pharmacokinetics ; blood pressure control
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The pharmacokinetics of nisoldipine have been studied after oral administration of one 10 mg tablet to 3 groups of patients: Group A (n=8) with a mean creatinine of 90 ml/min, Group B (n=8) with a mean creatinine clearance of 12 ml/min and Group C of 12 patients on maintenance haemodialysis. All of them were studied off-dialysis and 7 were also studied on a dialysis day. No significant differences were observed between Groups A, B and C (on an interdialysis day) in AUC (0–7h), tmax, Cmax and plasma protein binding. Unchanged nisoldipine could not be recovered from the urine in any patient. Haemodialysis did not significantly affect AUC, tmax and Cmax, and nisoldipine could not be detected in the dialysate. The results indicate that the dose of nisoldipine need not be changed in patients with renal dysfunction, and that a supplementary dose is not required after haemodialysis. Blood pressure in the uraemics fell more than in the patients with good renal function.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00614560
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  • 16
    Electronic Resource
    Electronic Resource
    Single- and multiple-dose pharmacokinetics of terodiline in geriatric patients (1988)
    Springer
    European journal of clinical pharmacology 34 (1988), S. 291-297 
    Details
    ISSN: 1432-1041
    Keywords: terodiline ; elderly patients ; pharmacokinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary As a target group, geriataric patients were selected for pharmacokinetic studies with terodiline (Mictrol), an anticholinergic and calcium antagonist drug effective in the treatment of urinary incontinence. The single-dose kinetics in the geriatric patients (mean age 82 years) differed significantly from that previously found (Hallén et al. 1987) in healthy volunteers (mean age 35 years). There were higher peak serum concentrations (110 vs 79 µg·l−1), increased half-life (189 vs 60 h), lower renal clearance (4.0 vs 10.9 ml·min−1) and lower total clearance (29 vs 75 ml·min−1). Multiple-doses of 12.5 mg b.d. for 6–8 weeks resulted in a mean steady-state concentration of 642 µg·l−1, which was in agreement with the single dose parameters. The studied geriatric patients can be characterized not only as old, but also as frail, bedridden, having several diseases and polymedicated. The differences in pharmacokinetics between younger and elderly subjects can be attributed to a variety of complex factors, which may alter the clearance and/or the volume of distribution.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00540958
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  • 17
    Electronic Resource
    Electronic Resource
    The influence of cholestyramine on the elimination of tenoxicam and piroxicam (1988)
    Springer
    European journal of clinical pharmacology 34 (1988), S. 283-289 
    Details
    ISSN: 1432-1041
    Keywords: piroxicam ; tenoxicam ; cholestyramine ; accelerated drug elimination ; pharmacokinetics ; healthy volunteers
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary We have studied the influence of multiple oral doses of cholestyramine on the single dose pharmacokinetics of tenoxicam and piroxicam in eight healthy young volunteers. Each subject received on two occasions single intravenous injections of 20 mg tenoxicam and on another two occasions single oral doses of 20 mg piroxicam. Both medications were followed by multiple oral doses of either cholestyramine or plain water (placebo). Compared with placebo cholestyramine accelerated the elimination of both drugs. The average values of half-lives were reduced (tenoxicam: 31.9 h vs 67.4 h; piroxicam: 28.1 h vs 46.8 h) due to increases in clearance. Cholestyramine-mediated enhancement of drug elimination was most pronounced in the subjects with a comparatively low baseline drug clearance. Thus, intersubject variability in clearance was smaller when the drug administrations were followed by the anion-exchange resin. The twofold acceleration of tenoxicam elimination in the present study in man contrasts with a much larger effect (five-fold) seen in experiments with dogs. This points to a much easier access of unchanged tenoxicam to the intestinal lumen in the dogs than in man. Comparing the pharmacokinetics of tenoxicam and piroxicam in the same volunteers revealed a high degree of correlation in clearance and half-lives and similar intersubject variabilities in mean kinetic variables.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00540957
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  • 18
    Electronic Resource
    Electronic Resource
    The pharmacokinetics of olsalazine sodium in healthy volunteers after a single i.v. dose and after oral doses with and without food (1988)
    Springer
    European journal of clinical pharmacology 34 (1988), S. 481-488 
    Details
    ISSN: 1432-1041
    Keywords: olsalazine sodium ; 5-ASA ; ac-5-ASA ; pharmacokinetics ; effect of food
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Olsalazine sodium (5,5′-azodisalicylic acid (OLZ)) was given to eight healthy volunteers as a 10 mg i.v. bolus dose and as a 1 g oral dose with and without food. To five fasting participants single oral doses of 2 g and 4 g were given. Blood and urine were collected during three weeks after each dose and were assayed for OLZ, a conjugate identified as a sulphate of OLZ (OLZs), 5-aminosalicylic acid (5-ASA), and N-acetyl-5-aminosalicylic acid (ac-5-ASA). The study showed that: 1. OLZ had a very short elimination half-life, mean 56 min. 2. OLZ was absorbed from the intestinal tract to a very small extent, as seen from the low systemic availability and low urinary excretion, 2.3% and 0.31% respectively, for a 1 g dose taken fasting. 3. OLZ was present in the serum partly as a conjugate, which was identified as an O-sulphate. Following the i.v. dose the serum half-life of the O-sulphate was estimated to be 7 days. 4. Food intake did not influence the systemic availability of OLZ and ac-5-ASA. 5. There was no dose-dependent increase of OLZ absorption with single doses up to 2 g, but a 4-g dose showed a more than two-fold increase in the individual peak serum concentration and in the systemic availability of OLZ. However, there was no significant increase in the mean residence time (MRT) for OLZ or in the serum concentration of either 5-ASA or ac-5-ASA at a dose of 4 g.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF01046706
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  • 19
    Electronic Resource
    Electronic Resource
    CSF and plasma pharmacokinetics of pethidine and norpethidine in man after epidural and intrathecal administration of pethidine (1988)
    Springer
    European journal of clinical pharmacology 34 (1988), S. 625-631 
    Details
    ISSN: 1432-1041
    Keywords: pethidine ; analgesics ; epidural-/intrathecal injection ; pharmacokinetics ; drug metabolism ; norpethidine ; adverse effects ; CSF drug levels
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The disposition of pethidine and its main metabolite, norpethidine, in cerebrospinal fluid (CSF) and plasma was studied in 11 thoracic surgery patients after lumbar epidural (100 mg;n=6) or lumbar intrathecal (25 mg;n=5) administration of pethidine. Pethidine appeared more slowly in plasma after intrathecal than after epidural administration (tmax 2.3 h and 14 min, respectively), but systemic bioavailability was similar. The CSF concentrations of pethidine were higher than those in plasma after both routes of administration. The maximal CSF/plasma concentration ratio was 6000 to 45000 after intrathecal administration but was only 26 to 97 after the epidural route. Pethidine was rapidly distributed in CSF; nine to ten h after the intrathecal and epidural injections the CSF/plasma concentration ratios were 12 to 89 and 2 to 33, respectively. The calculated bioavailability in CSF of epidural pethidine was 10.3%. The terminal elimination half-life of pethidine was 6.0 h (CSF) and 5.4 h (plasma) after intrathecal administration and 8.6 h (CSF) and 8.8 h (plasma) after epidural injection. The volume of distribution of unchanged pethidine in the subarachnoid space was 13 ml·kg−1 and clearance from the CSF was 15 µl·kg−1·min−1. In all patients receiving intrathecal pethidine and in some patients after epidural pethidine, CSF norpethidine concentrations were higher than those in plasma; the maximum CSF norpethidine was 102 to 1211 ng·ml−1 and 14 to 210 ng·ml−1 and the maximum CSF/plasma norpethidine concentration ratios were 21 to 652 and 0.6 to 14 times after intrathecal and epidural administration, respectively. Norpethidine was rapidly distributed and its level in CSF was about the same or lower than in plasma during the terminal elimination phase. The maximum CSF norpethidine level was 1.2±1.0% of that of pethidine after intrathecal injection. Thus, epidural pethidine enters the CSF more rapidly and to a greater extent than has been previously shown for epidural morphine, but pethidine is more rapidly redistributed from CSF. The terminal elimination half-life of pethidine was found to be long in relation to the reported duration of analgesia after a single spinal dose of pethidine, which suggests a potential risk of accumulation within the CSF on multiple spinal injections of pethidine. Pethidine is partly metabolised within the subarachnoid space by N-dealkylating enzymes in the CNS. After intrathecal injection of more than 25 mg pethidine, the concentration of the principle metabolite, norpethidine, in CSF may be higher than that associated with CNS toxicity in man.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00615228
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  • 20
    Electronic Resource
    Electronic Resource
    Doxazosin in patients with hypertension (1988)
    Springer
    European journal of clinical pharmacology 35 (1988), S. 21-24 
    Details
    ISSN: 1432-1041
    Keywords: doxazosin ; hypertension ; alpha-adrenergic blockade ; bioavailability ; pharmacokinetics ; adverse effects
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The antihypertensive effects and steady-state pharmacokinetics of doxazosin, as well as the bioequivalence of four dosage forms, were studied in 25 hypertensive patients. For an 8 mg daily dose mean Cmax at steady-state for all patients was 108 ng/ml; the mean tmax was 1.8 h. The mean terminal elimination half-life was 22 h. The four tablets containing 1, 2, 4, or 8 mg of doxazosin were bioequivalent in delivering the 8 mg dose. In patients with mild to moderate hypertension, 26-day treatment with doxazosin resulted in blood pressure reduction of 10/7 mm Hg in the supine and 13/18 mm Hg in the standing position. Adverse effects were generally mild and of brief duration.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00555502
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