Clinical Pharmacokinetics

, Volume 41, Issue 5, pp 329–342 | Cite as

How Important Are Gender Differences in Pharmacokinetics?

  • Bernd Meibohm
  • Ingrid Beierle
  • Hartmut Derendorf
Leading Article


Gender-related differences in pharmacokinetics have frequently been considered as potentially important determinants for the clinical effectiveness of drug therapy. The mechanistic processes underlying gender-specific pharmacokinetics can be divided into molecular and physiological factors.

Major molecular factors involved in drug disposition include drug transporters and drug-metabolising enzymes. Men seem to have a higher activity relative to women for the cytochrome P450 (CYP) isoenzymes CYP1A2 and potentially CYP2E1, for the drug efflux transporter P-glycoprotein, and for some isoforms of glucuronosyltransferases and sulfotransferases. Women were suggested to have a higher CYP2D6 activity. No major gender-specific differences seem to exist for CYP2C19 and CYP3A. The often-described higher hepatic clearance in women compared with men for substrates of CYP3A and P-glycoprotein, such as erythromycin and verapamil, may be explained by increased intrahepatocellular substrate availability due to lower hepatic P-glycoprotein activity in women relative to men.

Physiological factors resulting in gender-related pharmacokinetic differences include the generally lower bodyweight and organ size, higher percentage of body fat, lower glomerular filtration rate and different gastric motility in women compared with men.

Although gender disparity in pharmacokinetics has been identified for numerous drugs, differences are generally only subtle. For a few drugs, e.g. verapamil, β-blockers and selective serotonin reuptake inhibitors, gender-related differences in pharmacokinetics have been shown to result in different pharmacological responses, but their clinical relevance remains unproven. In contrast, gender differences of clinical importance have clearly been identified for pharmacodynamic processes such as QTc prolongation, and intensive future research efforts are needed to assess the full scope and impact of pharmacodynamic gender disparity on applied pharmacotherapy.


Clozapine Oral Clearance Fleroxacin Diflunisal Mizolastine 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.



The authors did not receive any funding in the preparation of this manuscript. There are no conflicts of interest directly relevant to the contents of this article.


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Copyright information

© Adis International Limited 2002

Authors and Affiliations

  • Bernd Meibohm
    • 1
  • Ingrid Beierle
    • 2
  • Hartmut Derendorf
    • 3
  1. 1.Department of Pharmaceutical SciencesCollege of Pharmacy, University of TennesseeMemphisUSA
  2. 2.Department of Clinical PharmacyCollege of Pharmacy, University of TennesseeMemphisUSA
  3. 3.Department of PharmaceuticsCollege of Pharmacy, University of FloridaGainesvilleUSA

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