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 been paid to this field despite at least theoretical reasons to believe that gender may be an important variable in the processes of absorption, distribution, metabolism, and excretion. Gastric acid secretion, gastrointestinal blood flow, proportions of muscular and adipose tissue, amount of drug binding proteins, gender-specific cytochrome P450 isozymes, physiologic and hormonal changes during the menstrual cycle, and renal blood flow are several factors that may contribute to sex-related differences in pharmacokinetics. Clinical investigations have documented greater absorption and subsequent incorporation of iron into erythrocytes, and higher bioavailability of ethanol in females. Women have been shown to have a slower metabolism of mephobarbital and propranolol but an increased biotransformation of methylprednisolone, all three 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-specific pharmacodynamic data are meager, evidence also supports the existence 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 males having an enhanced response compared to females. Pharmacokinetic and pharmacodynamic sex-related differences exist and are complex. Future research efforts should be designed to provide more gender-specific information on drug disposition and clinical effect.