Gender Differences in the Pharmacokinetics of Oral Dermatologic Medications

Abstract

Physiological differences exist between men and women that lead to different efficacy and side effect profiles of medications. Although some of this may be explained by differing pharmacodynamics, pharmacokinetic differences between the genders have been found for many medications. The oral dermatologic medications which have shown the most gender‐related differences are cyclosporine, erythromycin, and methotrexate. Cyclosporine and erythromycin are cleared faster in females, which may be due to either higher cytochrome P‐450 3A (CYP3A) activity in females or higher P‐glycoprotein levels in males. Methotrexate is cleared faster in males, which appears to be due to a higher glomerular filtration rate (GFR) and creatinine clearance in males. Gender differences in each pharmacokinetic parameter (absorption, distribution, metabolism, and excretion) have been described. Metabolism, in particular, varies greatly between the genders. Women clear substrates of CYP3A enzymes more rapidly than men, but it is debated whether this is a result of increased CYP3A activity in females or increased P‐glycoprotein in males. Most of the gender‐related differences in pharmacokinetics are considered important only for those medications with a low therapeutic index. In the future, drugs, such as cyclosporine, erythromycin, and methotrexate, may require different dosage recommendations, depending on gender.