Lack of interaction between nefazodone and cimetidine: a steady state pharmacokinetic study in humans.
The steady-state pharmacokinetic interaction between nefazodone and cimetidine was evaluated in a three-period crossover study consisting of three treatments of 1 week duration with a 1 week washout between treatments. The 18 healthy, male study subjects received: nefazodone hydrochloride 200 mg twice daily (every 12 h) for 6 days; cimetidine 300 mg four times daily for 6 days; and 200 mg nefazodone hydrochloride twice daily + 300 mg cimetidine four times daily for 6 days. On day 7 of each treatment, only the morning dose was administered. Serial blood samples were collected for pharmacokinetic analysis after drug administration on day 7 of each treatment; blood samples for trough levels (Cmin) to assess attainment of steady state, were also collected just prior to the morning doses on days 2-7 of each study period. Plasma samples were assayed for cimetidine, and nefazodone and its metabolites hydroxynefazodone and m-chlorophenylpiperazine by specific, validated h.p.l.c. methods. Statistical analyses of Cmin data indicated that, regardless of treatment, steady state was achieved for cimetidine by day 2 and for nefazodone and its metabolites by day 3 of multiple dosing, and that there were no significant differences in Cmin levels between treatments. When nefazodone and cimetidine were co-administered for 1 week, no change in steady-state pharmacokinetic parameters for cimetidine, nefazodone or hydroxynefazodone was observed compared with each drug dosed alone.(ABSTRACT TRUNCATED AT 250 WORDS)
Barbhaiya
R H
RH
Department of Metabolism and Pharmacokinetics, Bristol-Myers Squibb Pharmaceutical Research Institute, Princeton, NJ 08543-4000, USA.
Shukla
U A
UA
Greene
D S
DS
D000284:Administration, Oral; D000328:Adult; D000704:Analysis of Variance; D000928:Antidepressive Agents / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D002851:Chromatography, High Pressure Liquid; D002927:Cimetidine / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D018592:Cross-Over Studies; D004347:Drug Interactions; D006635:Histamine H2 Antagonists / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D006801:Humans; D008297:Male; D010879:Piperazines / Q000097:blood; D017366:Serotonin Receptor Agonists / Q000097:blood; D014230:Triazoles / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*
D000928:Antidepressive Agents; D006635:Histamine H2 Antagonists; D010879:Piperazines; D017366:Serotonin Receptor Agonists; D014230:Triazoles; C092333:hydroxynefazodone; C051752:nefazodone; D002927:Cimetidine; C015068:1-(3-chlorophenyl)piperazine