Single and multiple dose pharmacokinetics of nefazodone in subjects classified as extensive and poor metabolizers of dextromethorphan

British Journal of Clinical Pharmacology
R H BarbhaiyaD S Greene

Abstract

1. The single and multiple dose pharmacokinetics of nefazodone (NEF) and its active metabolites hydroxynefazodone (HO-NEF) and m-chlorophenyl-piperazine (mCPP) were evaluated in subjects classified as extensive metabolizers (EM) or poor metabolizers (PM) of dextromethorphan. 2. In a parallel design study, 10 subjects from each phenotype received either 50 mg or 200 mg oral doses of NEF as single doses on Day 1 and multiple (twice daily) doses on Days 12-22. 3. Serial plasma and urine samples were collected at specified time intervals after dosing on Days 1, 16, 18, 20 and 22. Plasma samples were analyzed for NEF, HO-NEF and mCPP. Urine samples were analyzed for mCPP and its metabolite p-hydroxy-mCPP (p-HO-mCPP) before and after hydrolyzing the samples with beta-glucuronidase. 4. For the 200 mg dose group, the single dose plasma results showed no significant differences in pharmacokinetic parameters for NEF and HO-NEF in EM compared with PM subjects. However, for mCPP, Cmax was 89 ng ml-1 in the PM subjects compared with 44 ng ml-1 in the EM subjects, AUC was higher in the PM than EM subjects (1642 ng ml-1 h and 412 ng ml-1 h, respectively), and mCPP elimination half-life increased from 6.1 h in the EM subjects to 16.4 h in the ...Continue Reading

Citations

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