Gender-related differences do exist in drug handling, but in general are relatively clinically insignificant. Theoretically, because of weight differences, women may receive more medication than men for a standard dose when converted to mg/kg. Greater effects might be expected from the range of normal weights rather than from the effects of gender.

Clinically significant gender effects have been reported with CNS, anti-inflammatory and cardiovascular drugs. It is suggested that women continue to be enrolled into most drug study programs, but that greater thought be given to obtaining 'representative' numbers in the early program planning stage. For drugs intended mainly or entirely for women, even Phase I testing in women should be usually considered. Single-dose testing, even in women of child-bearing potential, poses minimal risk if done early in the cycle, with adequate precautions and 'consort' consent to short sexual abstinence. Alternatively, women with tubal ligation could be enrolled for these small studies.

'Representative' could be twofold: a reflection of the percentage of women suffering from the disease, or a 'reasonable or sufficient' number to show clinically significant differences in efficacy or safety in the main efficacy and safety studies; alternatively, conducting at least one study just in women in Phase III. What is a 'clinically significant effect' would depend on the drug and disease, but effects with a less than 15% difference get harder to detect and generally will be less meaningful. Again, women of child-bearing potential could be included, depending on the age/prevalence of the disease. Women using oral contraceptives may be compared not only with males but also with non-OC users. OC and drug interaction studies are currently required for most drugs.

Early embryo drug exposure and the potential liability for any damage continues to influence industry, agencies, and some research workers. It must be recognized that, if an agent has human teratogenic potential, it is better to detect this before it achieves the marketplace. Unfortunately, this is unlikely to be detected because the small numbers of women becoming pregnant in any NDA program make it impossible to detect drug-induced effects from spontaneous birth defects. Data in women are needed and the possibility is suggested of an expanded National Register along the lines of the International Clearing House for Birth Defects Monitoring to follow up the expected small number of embryos exposed and a Compensation Panel in the event of proven damage, funded by an excise tax, as with vaccines.

Finally, with all the great strides being made to unravel the human genome and determine the gene structures and their influence, we are much nearer to tailoring drugs to match male and female differences, and with enhanced computer power, this chapter may become moot.

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