¹Departments of Clinical Pharmacy, Pharmacology, Biochemistry, and Neurology, National Cheng Kung University, Medical College, Tainan, Taiwan

Correspondence: Jin-ding Huang, PhD, Department of Pharmacology, National Cheng Kung University, Medical College, 1 University Road, Tainan 70101, Taiwan.

^*Supported by grants NSC84-2331-B006-045 from the National Sciences Council and DOH84-TD-044 from the Department of Health of the Republic of China (Taipei, Taiwan).

Received 20 November 1995; Accepted 8 April 1996.

Abstract

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 32 unrelated volunteers. Based on the genotypes, subjects were categorized into three groups: homozygous CC₁₈₈ (n = 8), heterozygous CT₁₈₈ (n = 12), and homozygous TT₁₈₈ (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 -glucuronidase. The total recovered amount of morphine and glucuronides was 4349 646, 2564 242, and 1127 164 nmol (mean SEM), respectively, for CC₁₈₈, CT₁₈₈, and TT₁₈₈ 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 TT₁₈₈ subjects. The results suggest a future study to assess the analgesic effect of codeine in different genotypes of CYP2D6 extensive metabolizers.