Pharmacokinetics of codeine and its metabolites in Caucasian healthy volunteers: comparisons between extensive and poor hydroxylators of debrisoquine.

摘要: 1. The kinetics of codeine and seven its metabolites codeine-6-glucuronide (C6G), norcodeine (NC), NC-glucuronide (NCG), morphine (M), M-3 (M3G) 6-glucuronides (M6G), normorphine (NM) were investigated after a single oral dose 50 mg phosphate in 14 healthy Caucasian subjects including eight extensive (EM) six poor (PM) hydroxylators debrisoquine. plasma urine concentrations the measured by h.p.l.c. 2. mean area under curve (AUC), half-life total clearance 1020 +/- 340 nmol l-1 h, 2.58 0.57 h 2.02 0.73 l h-1 kg-1, respectively. There no significant differences between EM PM these aspects. 3. had significantly lower AUC M3G, active M6G, NM M (P less than 0.0001), partial metabolic O-demethylation 0.0001). In contrast, higher NC 0.05) EM. was difference C6G NCG, nor clearances N-demethylation glucuronidation. 4. Among EM, 15 times that codeine, which turn M. AUCs M6G about 6 10 M, glucuronidation 8 12 those N- O-demethylations, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)