Gender has a small but statistically significant effect on clearance of CYP3A substrate drugs

J Clin Pharmacol. 2008 Nov;48(11):1350-5. doi: 10.1177/0091270008323754. Epub 2008 Aug 29.


The role of gender on the disposition of drugs metabolized by cytochrome P4503A (CYP3A) remains controversial. Some sources suggest that CYP3A activity in women exceeds that in men, but evidence to support this position is inconsistent at best. We evaluated 38 data sets in which clearance of CYP3A substrate drugs was studied in healthy young male and young female subjects. None of these drugs was a substrate for transport by P-glycoprotein (P-gp). The overall mean (+/-SE) for the female/male ratio of weight-normalized clearance was 1.26 (+/-0.07) for parenteral dosage and 1.17 (+/-0.07) for oral dosage. Both ratios were significantly different (P < .05) from 1.0. For oral dosage studies, the female/male clearance ratio was unrelated to the drug's absolute oral bioavailability. Thus gender has a small and statistically significant, although most likely clinically unimportant, influence on CYP3A phenotype for substrates not transported by P-gp.

Publication types

  • Research Support, N.I.H., Extramural
  • Review

MeSH terms

  • ATP Binding Cassette Transporter, Subfamily B, Member 1 / metabolism
  • Administration, Oral
  • Biological Availability
  • Biological Transport
  • Cytochrome P-450 CYP3A
  • Cytochrome P-450 Enzyme System / metabolism*
  • Female
  • Humans
  • Male
  • Pharmaceutical Preparations / administration & dosage
  • Pharmaceutical Preparations / metabolism*
  • Pharmacokinetics
  • Sex Factors


  • ATP Binding Cassette Transporter, Subfamily B, Member 1
  • Pharmaceutical Preparations
  • Cytochrome P-450 Enzyme System
  • CYP3A protein, human
  • Cytochrome P-450 CYP3A