FORMATION OF MORPHINE FROM CODEINE IN CHINESE SUBJECTS OF DIFFERENT C-GAMMA-P2D6 GENOTYPES

Codeine and morphine pharmacokinetics among different CYP2D6 genotypes was compared in this study. Polymerase chain reaction tests were used to determine CYP2D6 genotypes in leukocyte deoxyribonucleic acid in 3 2 unrelated volunteers. Based on the genotypes, subjects were categori zed into three groups: homozygous C/C-188 (n=8), heterozygous C/T-188 (n=12), and homozygous T/T-188 (n=12). Each subject was given a single oral dose of 30 mg codeine phosphate tablet after overnight fasting. Plasma concentration of codeine and 24-hour urinary morphine recovery were measured with HPLC. All three genotypes of subjects showed almost identical time profiles of plasma codeine. Urinary morphine glucuroni de was hydrolyzed with beta-glucuronidase. The total recovered amount of morphine and glucuronides was 4349+/-646, 2564+/-242, and 1127+/-16 4 nmol (mean+/-SEM), respectively, for C/C-188, C/T-188, and T/T-188 s ubjects (p <0.05). The significant lower amount of urinary morphine bu t identical codeine plasma concentration suggested a lower partial cle arance of the formation of morphine from codeine in T/T-188 subjects. The results suggest a future study to assess the analgesic effect of c odeine in different genotypes of CYP2D6 extensive metabolizers.