Formation of morphine from codeine in Chinese subjects of different CΥP2D6 genotypes

Codeine and morphine pharmacokinetics among different CΥP2D6 genotypes was compared in this study. Polymerase chain reaction tests were used to determine CΥP2D6 genotypes in leukocyte deoxyribonucleic acid in 32 unrelated volunteers. Based on the genotypes, subjects were categorized into three groups: homozygous C/C₁₈₈ (n = 8), heterozygous C/T₁₈₈ (n = 12), and homozygous T/T₁₈₈ (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 glucuronide was hydrolyzed with β-glucuronidase. The total recovered amount of morphine and glucuronides was 4349 ± 646, 2564 ± 242, and 1127 ± 164 nmol (mean ± SEM), respectively, for C/C₁₈₈, C/T₁₈₈, and T/T₁₈₈ subjects (p < 0.05). The significant lower amount of urinary morphine but identical codeine plasma concentration suggested a lower partial clearance of the formation of morphine from codeine in T/T₁₈₈ subjects. The results suggest a future study to assess the analgesic effect of codeine in different genotypes of CYP2D6 extensive metabolizers.