Formation of morphine from codeine in Chinese subjects of different CYP2D6 genotypes*

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 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 beta-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.

Differences in Drug Pharmacokinetics Between East Asians and Caucasians and the Role of Genetic Polymorphisms

“…The PMs had very low or undetectable concentrations of morphine. The partial clearance of morphine formation also showed a significant decreasing trend among homozygous CYP2D6*10, heterozygous CYP2D6*10, and reference Chinese 169 …”

Frequencies of CYP2D6 mutant alleles in a normal Japanese population and metabolic activity of dextromethorphan O‐demethylation in different CYP2D6 genotypes

“…Similarly, Tseng et al. [16] reported that the partial metabolic clearance of codeine to morphine in homozygotes for CYP2D6 * 10 is more than four times lower than that for the wild‐type. The findings suggest that the polymorphism produced by CYP2D6 * 10 play a more important role than previously thought in the treatment of Japanese patients with drugs metabolized by CYP2D6.…”

Ethnic Differences in Pain and Pain Management

“…Moreover, over the past three decades, pharmacogenetic research has found substantial differences among ethnic groups in the metabolism, clinical effectiveness and side-effect profiles of many drugs [45]; however, only a few studies have examined ethnic differences in the effects of pain medications. A pharmacokinetic study found ethnic differences (between non-Hispanic whites, African–Americans and Asian participants) in the effectiveness of codeine [46] and the metabolism of morphine may differ between non-Hispanic whites and Chinese patients [47]. Rabow and Dibble examined ethnic and country-of-origin differences in patients with terminal and end-stage chronic illness and found no differences in pain between Asian, African–American and Latino patients [48], although they reported significantly more pain than non-Hispanic whites.…”