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Tijdschrift voor Psychiatrie 43 (2001) 3, 163 - 171

Review article

Gender differences in pharmacokinetics and pharmacodynamics

A.H. Veefkind

background There is a lack of information about differences in the treatment responses of men and women to drugs because hitherto women have been underrepresented in clinical trials. It is becoming increasingly clear that the recommended dosage of a particular drug does not always match the dosage that an individual actually requires.
aims To identify the state of the art and to estimate the clinical relevance.
method This article reviews recent progress in the field of gender differences in pharmacokinetics and pharmacodynamics. Review of the literature was done by Medline searches with the keywords gender, pharmacokinetics, pharmacodynamics and cytochrome p450.
results The sex-dependent activity of cyp isoenzymes can cause major differences in the hepatic metabolism of drugs. Data indicate that cyp3a4, and possibly also cyp2d6, is more active in women than in men. As for cyp1a2 and cyp2c19, however, the effects are reverse: more active in men than in women. The use of hormonal contraceptives reduces the activity of cyp2c19 still further. The influence of oestrogens and progestagens has hardly been investigated, but substantial kinetic effects have been reported occasionally. The pharmacokinetic parameters need to be absolutely clear before any precise conclusion can be drawn about the more complicated pharmacodynamic parameters in vivo.
conclusion There are indications that prescription of identical doses for women and men may result in overdosing or underdosing, depending on the metabolic route.

keywords cytochrome p450, gender differences, pharmacodynamics, pharmacokinetics