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Gender Has a Small but Statistically Significant Effect on Clearance of CYP3A Substrate Drugs
Author(s) -
Greenblatt David J.,
Moltke Lisa L.
Publication year - 2008
Publication title -
the journal of clinical pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.92
H-Index - 116
eISSN - 1552-4604
pISSN - 0091-2700
DOI - 10.1177/0091270008323754
Subject(s) - cyp3a , pharmacology , medicine , substrate (aquarium) , biology , cytochrome p450 , metabolism , ecology
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.