GENDER DIFFERENCES IN HUMAN PHARMACOKINETICS AND PHARMACODYNAMICS

Gender differences in pharmacokinetics and pharmacodynamics have long been recognized in animals. In humans, however, little attention has b een paid to this field despite at least theoretical reasons to believe that gender may be an important variable in the processes of absorpti on, distribution, metabolism, and excretion. Gastric acid secretion, g astrointestinal blood flow, proportions of muscular and adipose tissue , amount of drug binding proteins, gender-specific cytochrome P450 iso zymes, physiologic and hormonal changes during the menstrual cycle, an d renal blood flow are several factors that may contribute to sex-rela ted differences in pharmacokinetics. Clinical investigations have docu mented greater absorption and subsequent incorporation of iron into er ythrocytes, and higher bioavailability of ethanol in females. Women ha ve been shown to have a slower metabolism of mephobarbital and propran olol but an increased biotransformation of methylprednisolone, all thr ee of which are metabolized by enzymes of the cytochrome P450 system. Lastly, the renal excretion of amantadine was inhibited significantly by quinidine and quinine in men but not in women. While gender-specifi c pharmacodynamic data are meager, evidence also supports the existenc e of sex-related differences. Women appear to be more prone to develop torsades de points from drugs such as quinidine and procainamide than men. A dimorphism in insulin sensitivity has been demonstrated with m ales having an enhanced response compared to females. Pharmacokinetic and pharmacodynamic sex-related differences exist and are complex. Fut ure research efforts should be designed to provide more gender-specifi c information on drug disposition and clinical effect.