今日の論文

• Goldstein, "Clinical relevance of genetic polymorphisms in the human CYP2C subfamily"
• Hiemke & Hartter, "Pharmacokinetics of selective serotonin reuptake inhibitors"
  • 今さらではありますが，いろいろ必要あって．

Diazepam, an anxiolytic drug is demethylated by CYP2C19.   Plasma half-lives of diazepam were dramatically longer in individuals genotyped as homozygous for the defective CYP2C19*2 allele (84 h) than in individuals who were homozygous for the wild-type CYP2C19*1 allele (20 h), or individuals heterozygous for one defective CYP2C19 allele (64 h).   The half-life of the metabolite desmethyldiazepam was also longer in homozygous CYP2C19 PMs.

CYP2D6 probably is involved as a low-capacity and high-affinity enzyme that has also been shown in vitro.   The saturability of the process might be caused by substrate inhibition, since paroxetine is a potent inhibitor of CYP2D6 and thus, of its own metabolism.   The contribution of other CYP isoenzymes besides CYP2D6 have so far not been documented.