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  • pharmacokinetics  (97)
  • Springer  (97)
  • 1990-1994  (95)
  • 1970-1974  (2)
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  • 1935-1939
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  • 1
    Electronic Resource
    Electronic Resource
    The effects of a salicylate, ibuprofen, and naproxen on the disposition of methotrexate in patients with rheumatoid arthritis (1992)
    Springer
    European journal of clinical pharmacology 42 (1992), S. 121-125 
    Details
    ISSN: 1432-1041
    Keywords: Methotrexate ; non-steroidal anti-inflammatory drugs (NSAIDs) ; interaction ; disposition ; adverse effects ; pharmacokinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary We have studied the pharmacokinetics of methotrexate in patients with rheumatoid arthritis concurrently treated with choline magnesium trisalicylate, ibuprofen, naproxen, or a non-NSAID analgesic (control treatment). The apparent systemic clearance of methotrexate was significantly reduced by all three treatments. Trisalicylate and ibuprofen both significantly reduced methotrexate renal clearance, but only the trisalicylate significantly displaced methotrexate from protein, increasing the fraction unbound by 28%. These data show that NSAIDs can affect the disposition of methotrexate, possibly increasing the potential for toxicity and necessitating dosage adjustments. However, large inter-subject variability precludes specific dosage recommendations.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00278469
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  • 2
    Electronic Resource
    Electronic Resource
    Pharmacokinetics and Pharmacodynamics of L-703,014, a Potent Fibrinogen Receptor Antagonist, After Intravenous and Oral Administration in the Dog (1994)
    Springer
    Pharmaceutical research 11 (1994), S. 426-431 
    Details
    ISSN: 1573-904X
    Keywords: fibrinogen receptor antagonist ; pharmacokinetics ; pharmacodynamics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Abstract The pharmacokinetics and pharmacodynamics of L-703,014, a fibrinogen receptor antagonist, have been examined in the dog. An analytical method which utilizes methanol precipitation of dog plasma proteins followed by HPLC with an automated column switching technique using the chemical analogue L-704,326 as internal standard was developed for the determination of L-703,014 in dog plasma. The compound was not metabolized in the dog and was eliminated in the kidneys and into bile. Of the administered dose, 68.9 ± 1.3% (i.v.) and 80.5 ± 11.9% (p.o.) were recovered in the feces; 20.3 ± 3% (i.v.) and 2.2 ± 0.2% (p.o.) were recovered in the urine by 72 hr. L-703,014 was 23 ± 3.4% bound in dog plasma protein and the mean ratio of plasma/whole blood was 1.22 ± 0.05. The mean terminal half-life was 118 ± 36 min, the mean steady-state volume of distribution was 0.61 ± 0.22 L/kg, and the mean plasma clearance was 8 ± 2 mL/min/kg. Ex vivo platelet aggregation measurements were made by inducing platelet aggregation with 10 µg/ mL collagen in the presence of 1 µM epinephrine as an agonist. The mean C 50 was 44.4 ± 6.0 ng/mL, and the mean Hill coefficient was 1.5 ± 0.3. The mean bioavailability was 4.9 ± 1.4% in dogs administered 2.0 mg/kg (p.o.).
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1018973323039
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  • 3
    Electronic Resource
    Electronic Resource
    A phase I clinical and pharmacokinetic study of the oral and the oral/ intravenous administration of menogaril (1993)
    Springer
    Investigational new drugs 11 (1993), S. 17-27 
    Details
    ISSN: 1573-0646
    Keywords: menogaril ; phase I ; pharmacokinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Thirty-five patients with advanced refractory cancer were enrolled on this phase I study of menogaril administered orally every 4 weeks at dosages ranging from 85 mg/m2 to 625 mg/m2. An additional 12 patients received alternating oral and IV doses of menogaril (250 mg/m2 IV; 250–500 mg/m2 oral) with accompanying blood and urine sampling for pharmacokinetics analysis. Nausea and vomiting were the dose-limiting toxicities at the 625 mg/m2 dosage level; vomiting was inadequately relieved by prophylactic antiemetics at this dosage level. Other toxicities included sporadic leukopenia at all dosage levels; at dosages of 500 mg/m2 and 625 mg/m2, leukopenia 〈 3000/μl occurred in 7 of 24 patients. Anemia and thrombocytopenia were much less frequent toxicities. Among the patients receiving IV menogaril, peripheral vein phlebitis, leukopenia and anemia were the predominant toxicities. No antitumor responses were observed, yet one patient with nonsmall cell lung cancer experienced a 30% reduction in metastatic tumor nodules. For the patients receiving alternating oral and IV menogaril, comparative pharmacokinetic analyses were performed by HPLC. After oral administration, maximum plasma concentrations were achieved in an average of 6 hours; maximum plasma concentrations were less than one-quarter of those achieved after intravenous administration. The harmonic mean (±SD) terminal disposition half-life after oral dosing was 29.3 ±9.2 hours; mean systemic bioavailability was 33.6±10.5% after oral dosing. Forty-eight hours after an oral dose, mean cumulative urinary excretions of menogaril and the primary metabolite, N-demethylmenogaril, were 4.00±0.96% and 0.44±0.16%, respectively. Because of the poor tolerance of oral menogaril and minimal evidence of biological activity, this schedule of drug administration is not recommended for phase II evaluation. Based on this and other published studies of oral menogaril, frequent chronic low-intermediate dosages of the drug may be given orally with potentially better tolerance and antitumor activity.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00873906
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  • 4
    Electronic Resource
    Electronic Resource
    Effect of ampicillin on mefloquine pharmacokinetics in thai males (1991)
    Springer
    European journal of clinical pharmacology 40 (1991), S. 631-633 
    Details
    ISSN: 1432-1041
    Keywords: Mefloquine ; ampicillin ; Thai subjects ; pharmacokinetics ; enterohepatic recycling ; drug interaction ; adverse effects
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The kinetics of a single oral dose of mefloquine given either alone or with ampicillin has been studied in 8 healthy Thai male volunteers. There was a significantly higher maximum whole blood mefloquine concentration after coadministration with ampicillin (1648 vs 1228 ng·ml−1), as well as a significantly reduced terminal half life (15.3 vs 17.7 days), mean residence time (20.1 vs 23.4 days) and volume of distribution at steady state (14.1 vs 19.4 l·kg−1). Although there was no significant change in the AUC from zero time to infinity, the AUC from zero time to 5 days was significantly increased by ampicillin (4.86 vs 3.27 μg·ml−1 day). These changes in mefloquine disposition after antibiotic treatment may be due both to an increase in fractional bioavailability and a reduction in the enterohepatic recycling of mefloquine.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00279985
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  • 5
    Electronic Resource
    Electronic Resource
    The pharmacokinetics and pharmacodynamics of fosinopril in haemodialysis patients (1993)
    Springer
    European journal of clinical pharmacology 45 (1993), S. 431-436 
    Details
    ISSN: 1432-1041
    Keywords: Fosinopril ; ACE inhibitors ; haemodialysis ; pharmacokinetics ; pharmacokinetics-pharmacodynamics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The pharmacokinetics and pharmacodynamics of fosinoprilat, the diacid of fosinopril sodium (a new angiotensin-converting enzyme (ACE) inhibitor), were investigated in six haemodialysis patients. Intravenous 14C-fosinoprilat (7.5 mg), oral 14C-fosinopril sodium (10 mg) and oral fosinopril sodium (10 mg) were administered in an open-label, randomized study. Mean maximum concentration (Cmax), clearance (CL), volume of distribution at steady-state (Vss), mean residence time (MRTiv), and t1/2 values after IV administration of 14C-fosinoprilat were 2,042 μg·ml−1, 11.3 ml·min−1, 11.01, 16.3 h and 28.3 h, respectively. Following oral administration of 14C-fosinopril, mean Cmax, time to maximum plasma concentration (tmax), and fosinoprilat bioavailability values were 197 ng·ml−1, 5.2 h and 29.2 %. Para-hydroxy fosinoprilat and fosinoprilat glucuronide comprised approximately 15 % and 2 % of radioactivity recovered in faeces. Four hours of haemodialysis only cleared approximately 1.5 % of the administered dose. The maximum effect (Emax) model was fitted to the percentage inhibition of serum ACE activity vs. fosinoprilat concentration data in three patients. Emax ranged from 95.3 to 102.5 %, and IC50 (the fosinoprilat concentration required to produce 50 % of Emax) ranged from 2.6 to 4.2 ng·ml−1. Pharmacokinetic variables of the patients were similar to those in patients with moderate to severe renal dysfunction. Dosage modifications or supplemental dosing following dialysis are unnecessary.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00315514
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  • 6
    Electronic Resource
    Electronic Resource
    Pharmacokinetics and tolerability of ascending intravenous doses of granisetron, a novel 5-HT3 antagonist, in healthy human subjects (1994)
    Springer
    European journal of clinical pharmacology 46 (1994), S. 159-162 
    Details
    ISSN: 1432-1041
    Keywords: Granisetron ; Anti-emetic ; pharmacokinetics ; tolerance ; ascending dose ; healthy subjects
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Abstract The pharmacokinetics and tolerance of granisetron, a novel 5HT3-receptor antagonist which is under development as an anti-emetic agent have been studied after administration of single 30 min intravenous infusions to three groups of 8 healthy male subjects, in a series of placebo-controlled ascending dose studies (50, 80, 100 and 130 μg·kg−1 to group 1; 150, 180, 200 and 230 μg·kg−1 to group 2 and 270 and 300 μg·kg−1 to group 3). Plasma and urine samples were analysed for granisetron by HPLC with fluorimetric detection. Administration of granisetron was well tolerated by the volunteers and there were no serious adverse effects reported. Pharmacokinetic parameters and dose-normalised plasma levels appeared to be independent of dose in the range 50 to 300 μg·kg−1, although there was extensive inter-subject variability. Granisetron was extensively distributed, with mean volumes of distribution ranging from 186–264 l at the various doses. Total plasma clearance was, in general, rapid (mean values of 37.0 to 49.9 l·h−1) and predominantly non-renal, with most subjects excreting less than 20% of the dose unchanged in urine. Mean t1/2 values ranged from 4.1 to 6.3 h and MRT from 5.2 to 8.1 h.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00199881
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  • 7
    Electronic Resource
    Electronic Resource
    Effect of concomitant administration of cimetidine and ranitidine on the pharmacokinetics and electrocardiographic effects of terfenadine (1993)
    Springer
    European journal of clinical pharmacology 45 (1993), S. 41-46 
    Details
    ISSN: 1432-1041
    Keywords: Terfenadine metabolism ; cimetidine ; ranitidine ; antihistamines ; Torsades de Pointes ; pharmacokinetics ; drug interaction
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Terfenadine is a widely prescribed non-sedating antihistamine which undergoes rapid and almost complete first pass biotransformation to an active carboxylic acid metabolite. It is unusual to find unmetabolised terfenadine in the plasma of patients taking the drug. Terfenadine in vitro is a potent blocker of the myocardial potassium channel. Overdose, hepatic compromise and the coadministration of ketoconazole and erythromycin result in the accumulation of terfenadine, which is thought to be responsible of QT prolongation and Torsades de Pointes ventricular arrhythmia in susceptible individuals. Cimetidine and ranitidine are two popular H2 antagonists which are often taken with terfenadine. The effects of cimetidine and ranitidine on terfenadine metabolism were studied in two cohorts of 6 normal volunteers given the recommended dose of terfenadine (60 mg every 12 h) for 1 week prior to initiation of cimetidine 600 mg every 12 h or ranitidine 150 mg every 12 h. Pharmacokinetic profiles and morning pre-dose electrocardiograms were obtained whilst the patients were on terfenadine alone and after the addition of cimetidine or rantidine. One of the subjects in each cohort had a detectable plasma level of parent compound after 1 week of terfenadine therapy alone; it did not accumulate further after addition of the H2 antagonist. The pharmacokinetics of the carboxylic acid metabolite of terfenadine (Cmax, tmax, AUC) were not significantly changed after co-administration of either H2 antagonist. None of the remaining 5 subjects in either cohort demonstrated accumulation of unmetabolised terfenadine after addition of the respective H2 antagonist and electrocardiographic QT intervals and T-U morphology in them was not changed during the course of the study. We conclude that cimetidine and ranitidine in the dosages used in this study did not affect the metabolism of terfenadine, and that patients exposed to these drug combinations are not at increased risk of altered cardiac repolarisation.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00315348
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  • 8
    Electronic Resource
    Electronic Resource
    Interaction of ORG 10172, a low molecular weight heparinoid, and digoxin in healthy volunteers (1991)
    Springer
    European journal of clinical pharmacology 41 (1991), S. 245-250 
    Details
    ISSN: 1432-1041
    Keywords: Org 10172 ; Digoxin ; heparinoid ; pharmacokinetics ; pharmacodynamics ; drug interactions
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Potential pharmacokinetic and pharmacodynamic interactions between a new low molecular weight heparinoid Org 10172 (bolus injection of 3250 anti-Xa units) and digoxin (0.25 mg once daily for 8 days) were studied in 6 healthy male volunteers using an open, randomised three-way cross-over design. Digoxin produced a slight increase in clearance of anti-Xa activity from 4.3 to 4.8 ml·min−1, while plasma anti-thrombin and thrombin generation inhibiting (TGI) activity remained unchanged. Digoxin did not affect the actions of Org 10172 on the clotting tests. In the presence of Org 10172 there was a reduction in the AUC of digoxin during one dosing interval after the seventh digoxin tablet from 20 to 17 ng·ml−1·h, and a significant reduction in the average serum digoxin conentration. Since renal digoxin clearance was not significantly changed this probably might be due to a change in the non-renal clearance of digoxin. Atrio-ventricular node conduction, as measured by PR-time intervals, remained unchanged during all three treatments. In conclusion, although the pharmacokinetics of Org 10172 and digoxin were slightly changed by the combination, it is probably safe to administer Org 10172 and digoxin simultaneously. The clinical relevance of the slight decrease in plasma anti-Xa activity levels cannot yet be defined.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00315437
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  • 9
    Electronic Resource
    Electronic Resource
    High dose oral methylprednisolone in patients with rheumatoid arthritis: pharmacokinetics and clinical response (1992)
    Springer
    European journal of clinical pharmacology 42 (1992), S. 85-88 
    Details
    ISSN: 1432-1041
    Keywords: Methylprednisolone ; Rheumatoid arthritis ; bioavailability ; pharmacokinetics ; clinical response ; pulse steroid therapy
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary A commercially available 1.0 g intravenous (i.v.) dosage formulation of methylprednisolone, as the sodium hemisuccinate salt (Solu MedrolR, Upjohn) was administered both parenterally and orally (pulse steroid therapy) on separate occasions, to eight elderly (mean 65 y) patients with active rheumatoid arthritis. The relative oral bioavailability of the sterol was 69.2%. Elimination of methylprednisolone was prolonged when given orally; the mean residence times were 7.23 h and 3.94 h for oral and i.v. administrations, respectively. Clinical response to pulse steroid therapy was no different with respect to route of administration. There were no significant differences in standard clinical and laboratory assessments of disease activity when the two therapies were compared. Oral administration of methylprednisolone in patients requiring high-dose pulse steroid therapy is convenient and avoids the discomfort and inconvenience associated with i.v. administration.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00314925
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  • 10
    Electronic Resource
    Electronic Resource
    Stereoselective pharmacokinetics of oral nitrendipine in elderly hypertensive patients with normal and impaired renal function (1992)
    Springer
    European journal of clinical pharmacology 42 (1992), S. 423-427 
    Details
    ISSN: 1432-1041
    Keywords: Nitrendipine ; enantiomers ; stereoselectivity ; Renal failure ; pharmacokinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The pharmacokinetics of the enantiomers of nitrendipine has been studied in seven elderly patients with chronic renal failure (CRF) and in six control subjects (mean creatinine clearance 30 and 97 ml·min−1 respectively). Racemic nitrendipine 20 mg was given once daily for seven days and the pharmacokinetics of the enantiomers over the last dosage interval were determined using a stereospecific assay. In both groups nitrendipine exhibited stereoselective pharmacokinetics (AUC, Cmax), but the half-lives of the enantiomers did not differ in individual subjects. As an index of stereoselectivity, the mean S/R ratio of AUCs in control subjects (2.07) was not significantly different from the ratio in patients with CRF (2.68). The mean AUCs of (S)- and (R)-nitrendipine during the last dosage interval were increased in CRF by 132% and 85%, respectively. The observed doubling of the half-lives and the increases in Cmax did not reach significance because of the large variability in each group. Thus, the pharmacokinetics of oral nitrendipine is altered in CRF, but there was no change in the stereoselectivity of its pharmacokinetics.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00280129
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