Why should drugs be tested in both males and females? Because physiological differences between males and females affect drug activity. Factors like body weight, GI motility, intestinal enzyme activity, and kidney clearance rate affect how drugs move through the body and affect the absorption, excretion, distribution and metabolism of a drug in men and women differently. A drug’s mechanism of action may also impact men and women differently. For example, men and women react differently to many antidepressants, antipsychotic agents, and pain killers. Sometimes the fix is a simple change in dosage (like the FDA recommended for Ambien recently). In other cases, the cause may be more complex due to hormonal differences, gene expression or metabolism.
In the past, even after years of testing, it was not until a drug actually got into circulation that we found out if there were sex differences (when patients reported adverse effects!). But we hope that process will soon change. Early this month, the NIH announced that all researchers must included both male and female cells or animals in preclinical research. The expectation is that sex differences (or lack of differences) will be identified early in the discovery pipeline—before the drug is used in humans. Most drugs used today were studied predominately in males. In the long run, finding differences early will not only be cheaper, it will reduce the number of potential adverse effects in humans.
We have two standards for shoe sizing in men and women in the US and some other countries, should we do the same for drugs???