Clinical pharmacology and therapeutics
-
Clin. Pharmacol. Ther. · May 1999
Clinical TrialClinical pharmacokinetics of encapsulated oral 9-aminocamptothecin in plasma and saliva.
To study the pharmacokinetics and pharmacodynamics of the novel topoisomerase I inhibitor and antitumor agent 9-amino-20(S)-camptothecin in patients with solid tumors after repeated oral administration. ⋯ Our data indicate that the large interindividual pharmacodynamic variability in response to 9-aminocamptothecin is caused mainly by a variability in kinetic characteristics, suggesting that a kinetic-dynamic guided study design is warranted in future clinical investigations.
-
Clin. Pharmacol. Ther. · Apr 1999
Randomized Controlled Trial Clinical TrialThe effect of rifampin on the pharmacokinetics of oral and intravenous ondansetron.
Ondansetron is an antiemetic agent metabolized by cytochrome P450 (CYP) enzymes. Rifampin (INN, rifampicin) is a potent inducer of CYP3A4 and some other CYP enzymes. We examined the possible effect of rifampin on the pharmacokinetics of orally and intravenously administered ondansetron. ⋯ Rifampin considerably decreases the plasma concentrations of ondansetron after both oral and intravenous administration. The interaction is most likely the result of induction of the CYP3A4-mediated metabolism of ondansetron. Concomitant use of rifampin or other potent inducers of CYP3A4 with ondansetron may result in a reduced antiemetic effect, particularly after oral administration of ondansetron.
-
Clin. Pharmacol. Ther. · Jan 1999
Pharmacokinetics of meropenem in critically ill patients with acute renal failure undergoing continuous venovenous hemofiltration.
Meropenem is a broad-spectrum antibiotic used for severe infections. In patients with chronic end-stage renal failure, meropenem clearance is reduced and doses must be adjusted according to the creatinine clearance. The aim of this study was to assess pharmacokinetic data of meropenem in patients with acute renal failure and to determine the amount of drug removed by continuous venovenous hemofiltration, an often-used renal replacement therapy in patients with acute renal failure. ⋯ Pharmacokinetic data of anuric patients with acute renal failure were similar to those of patients with end-stage renal failure. Because hemofiltration contributes significantly to meropenem elimination, the recommended dose for critically ill anuric patients receiving continuous venovenous hemofiltration should be increased by 100% to avoid potential underdosing.
-
Clin. Pharmacol. Ther. · Jan 1999
Randomized Controlled Trial Clinical TrialAnalgesic efficacy of a combination of hydrocodone with ibuprofen in postoperative pain.
Two randomized, double-blind, parallel-group single-dose 2 x 2 factorial analgesic studies compared a single-dose or a 2-tablet dose of a combination of 7.5 mg hydrocodone bitartrate with 200 mg ibuprofen with each constituent alone and with a placebo in women with moderate or severe postoperative pain from abdominal or gynecologic surgery. A nurse-observer recorded patient reports of pain intensity and pain relief periodically for 8 hours. ⋯ The combination was likewise significantly superior to both hydrocodone and ibuprofen for most of these summary measures of analgesia. In a factorial analysis, both the hydrocodone and ibuprofen effects were significant for most summary measures of analgesia, whereas results of the interaction contrast were consistent with the concept that the analgesic effect of the combination represents the additive analgesia of its 2 constituents.