Interindividual and interethnic differences in the demethylation and glucuronidation of codeine

Br J Clin Pharmacol. 1989 Dec;28(6):629-37. doi: 10.1111/j.1365-2125.1989.tb03555.x.

Abstract

1. The 8 h urinary excretion of codeine and seven of its metabolites was compared in 149 healthy Swedish Caucasians and 133 healthy Chinese following a single oral dose of 25 mg codeine phosphate. 2. The total 8 h urinary recovery of drug-related material was 74 +/- 24% in the Caucasians and 60 +/- 14% in the Chinese (P less than 0.001). The excretion of unchanged codeine was significantly higher in the Chinese (7.2%) compared with the Caucasians (4.3%, P less than 0.001). 3. The Caucasians excreted significantly greater proportions of codeine-6-glucuronide (C6G) (62%) than the Chinese (44%) (P less than 0.001). The frequency distribution of the log metabolic ratio (MR) for glucuronidation (codeine/C6G) was shifted towards higher values in the Chinese population. Males in both groups and Chinese smokers had significantly lower glucuronidation MRs than females and non-smokers in the respective populations (P less than 0.001). 4. The frequency distribution of the MR for O-demethylation (codeine/morphine (M) + M-3 and M-6-glucuronide (M3G and M6G) + normorphine (NM) was highly skewed in the Caucasians, suggestive of a bimodal distribution. There was a 160-fold interindividual variation in this MR. A unimodal distribution of the log O-demethylation MR was observed in Chinese. The Caucasians excreted less M and more M6G than did the Chinese (P less than 0.001). 5. Significantly more norcodeine (NC) and less NC-glucuronide (NCG) were excreted in the Chinese compared with the Caucasians (P less than 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Asian Continental Ancestry Group
  • Codeine / metabolism*
  • Contraceptives, Oral, Hormonal / adverse effects
  • Dealkylation
  • Ethnic Groups
  • European Continental Ancestry Group
  • Female
  • Glucuronates / metabolism
  • Humans
  • Individuality
  • Male
  • Middle Aged
  • Sex Factors
  • Smoking / metabolism

Substances

  • Contraceptives, Oral, Hormonal
  • Glucuronates
  • Codeine