MadSci Network: Medicine
Query:

Re: Does the dosage of certain drugs depend on gender?

Date: Mon Mar 14 09:28:12 2005
Posted By: Michael Weaver, Staff, Biology/Microbiology, Merck & Co., Inc.
Area of science: Medicine
ID: 1110761155.Me
Message:

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.


References:

Gender Differences in the Pharmacokinetics of Oral Dermatologic 
Medications, Douglas J. Fife and Howard I. Maibach, Journal of 
Toxicology  Cutaneous and Ocular Toxicology , Volume 23 , Issue 2. June 
1, 2004.

Gender-Specific Drug Effects, Max Sherman, BSPharm, Pharmacy Times, 2003.


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