Correlation of tramadol pharmacokinetics and CYP2D6*10 genotype in Malaysian subjects

J Pharm Biomed Anal. 2002 Sep 5;30(2):189-195. doi: 10.1016/s0731-7085(02)00214-5.

Abstract

The aim of the present study is to investigate the influence of the CYP2D6*10 allele on the disposition of tramadol hydrochloride in Malaysian subjects. A single dose of 100 mg tramadol was given intravenously to 30 healthy orthopaedic patients undergoing various elective surgeries. After having obtained written informed consents, patients were genotyped for CYP2D6*10: the most common CYP2D6 allele among Asians by means of allele-specific polymerase chain reaction. The presence of other mutations (CYP2D6*1, *3, *4, *5, *9 and *17) was also investigated. Tramadol was extracted from 1 ml serum with an n-hexane: ethylacetate combination (4:1) after alkalinisation with ammonia (pH 10.6). Serum concentrations were measured by means of high-performance liquid chromatography. The pharmacokinetics of tramadol was studied during the 24 h after the dose. As among other Asians, the allele frequency for CYP2D6*10 among Malaysians was high (0.43). Subjects who were homozygous for CYP2D6*10 had significantly (P=0.046) longer mean serum half-life of tramadol than subjects of the normal or the heterozygous group (Kruskal-Wallis test). When patients were screened for the presence of other alleles, the pharmacokinetic parameter values were better explained. CYP2D6 activity may play a main role in determining tramadol pharmacokinetics. The CYP2D6*10 allele particularly was associated with higher serum levels of tramadol compared with the CYP2D6*1 allele. However, genotyping for CYP2D6*10 alone is not sufficient to explain tramadol disposition.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Asian People / genetics
  • Chi-Square Distribution
  • Cytochrome P-450 CYP2D6 / genetics*
  • Female
  • Gene Frequency / genetics
  • Genotype
  • Humans
  • Malaysia
  • Male
  • Middle Aged
  • Prospective Studies
  • Statistics, Nonparametric
  • Tramadol / blood
  • Tramadol / pharmacokinetics*

Substances

  • Tramadol
  • Cytochrome P-450 CYP2D6