GENDER DIFFERENCES IN PHARMACOKINETICS

There is growing awareness that the underrepresentation of women in cl inical trials and in particular in phase I studies may lead to incorre ct handling of drugs. Despite the fact that investigations are not per formed in a systematic way, there are a number of examples showing pha rmacokinetic differences between gender. From the data actually presen ted, it can be concluded that the activity of CYP 3A4 activity as meas ured by elimination in vivo is higher in women compared to men. CYP is oenzymes other than CYP 3A4 seem to be more active in men than in woma n, as are conjugation reactions, such as glucuronidation. The influenc e of changing hormonal levels during the lifetime of a woman has been looked at in some drugs but deserves further systematic investigation. The use of oral contraceptives can interfere with the metabolism of m any drugs whereas, in pregnancy, the elimination of antiepileptics is increased which, without dose adjustment, leads to an increased number of seizures. The impacts of hormonal replacement therapy (HRT) on the pharmacokinetics of concomitantly given drugs is an important issue, as HRT is increasingly used, but more research is needed in this field .