GENDER EFFECTS IN PHARMACOKINETICS AND PHARMACODYNAMICS

There are a number of examples of sex differences in drug pharmacokine tics and pharmacodynamics. Recent advances in the characterisation of specific isozymes involved in drug metabolism now allow for the prelim inary identification of enzyme systems that are affected by sex, While current data are somewhat limited and not in complete ageement, the m ajority of studies show that apparent cytochrome P450 (CYP) 3A4 activi ty is higher in women than in men, whereas the activity of many other systems involved in drug metabolism may be higher in men than in women . Women and men also show different pharmacodynamic responses to a var iety of drugs, While the clinical significance of these sex difference s remains to be determined, we anticipate that they will be most impor tant in the administration of drugs that have a narrow therapeutic ran ge, In addition, sex differences in drug metabolism may be involved in the higher incidence of adverse reactions to drugs in women compared with men. Further research is needed to determine the scope and signif icance of these sex differences. Female-specific issues such as pregna ncy, menopause, oral contraceptive use and menstruation may also have profound effects on drug metabolism. These effects can often be clinic ally important. Pregnancy may increase the elimination of antiepilepti c agents, reducing their efficacy. Oral contraceptive use can interfer e with the metabolism of many drugs and, conversely, certain drugs can impair contraceptive efficacy. More research is needed to determine t he impact of menopause, hormone replacement and menstruation on drug t herapy.