Posted by
Adele Lucchelli - Working Group on Aging
Dipartimento di Farmacologia Sperimentale ed Applicata
Università di Pavia
Viale Taramelli 14
27100 Pavia
adele.lucchelli@unipv.it

Gender-related differences have been reported in the activity of CYP isoforms, which can differently affect drug metabolism in male and female.
Referring to the different CYP isoforms no clear-cut evidences have been found and the question of the role of gender on CYP mediated drug disposition is still controversial.
Recently, Greenblatt and von Moltke¹ reviewed the role of gender in the disposition of drugs by the CYP3A family, choosing only studies on drugs which are not substrates of the P-gp transporter protein [eg, selected benzodiazepines (adinazolam, alprazolam, bromazepam, clobazam, midazolam,triazolam), antidepressants (nefazodone, trazodone), calcium entry blockers (nifedipine, nimodipine)] in young males and females. They found that weight-normalized clearance of such drugs, mainly biotransformed by CYP3A is 20%-30% higher in women than in men, both for parenteral and oral dosage. However this difference is unlikely to be clinically important since when a fixed dose is administered to both women and men the slightly higher weight-normalized clearance in women will be offset by their lower average body weight. Moreover, a great variability in male/female differences were found among studies using the same drug (eg, oral triazolam) thus concluding that gender differences in CYP3A activity are unlikely to be clinically important.
Sinues et al²in a young Spanish population based-study, found that sex presented a borderline influence on CYP2A6 activity, measured by the urinary metabolites ratio of caffeine, with women having more elevated CYP2A6 ratio in relation to men. But, when women using oral contraceptives were considered it was found that they had a strikingly higher CYP2A6 activity than women not using oral contraceptives or men. Therefore, slight gender differences in CYP2A6 activity in a young population can become significant if women are treated with gender-specific drugs affecting the female hormonal status.

Articles’ abstract available at:
http://www.ncbi.nlm.nih.gov/pubmed/18757784?ordinalpos=4&itool=EntrezSys...
http://www.ncbi.nlm.nih.gov/pubmed/18715882?ordinalpos=1&itool=EntrezSys...

• ¹Greenblatt DJ, von Moltke LL. Gender has a small but statistically effect on clearance of CYP3A substrate drugs. J. Clin. Pharmacol. 2008, Nov,48,1350-5
• ²Sinues B, Fanlo A, Mayayo E, Carcas C, Vicente J, Arenaz I, Cebollada A. CYP2A6 activity in an healthy Spanish population: effect of age, sex, smoking and oral contraceptives. Hum. Exp. Toxicol. 2008, May, 27, 367-72