Pharmacodynamics and Pharmacokinetics : Sex-Specific Conditions
Sex-specific issues such as use of oral contraceptives or pregnancy may produce a clinically significant change in drug metabolism in a relatively short time, may result in toxic or sub-therapeutic levels of drug with narrow therapeutic ranges, and may require dosage adjustment. Menopause also may cause clinically significant changes in drugs clearance but the underlying mechanism is not known.38
Oral contraceptives (OCs) are among the most widely prescribed drugs in the world. While certain drugs can affect the metabolism of OCs,39 OCs can affect the metabolism of other drugs through two mechanisms. First, OCs ethinyl-containing steroids are suicide inactivators of cytochromes P450, including CYP3A4. OCs could reduce hepatic clearance of drugs such as cyclosporine, corticosteroids, and theophylline by as much as 30%. Second, OCs have been shown to increase levels of glucuronosyl transferase. A study found conjugation of acetaminophen to be 48% greater in women who used OCs than in those who did not. Increases in clearance of oxazepam, temazepam, morphine, clofibric acid, and aspirin have been observed due to increased conjugation when these drugs are co-administered with OCs.40
