Interactions with oral contraceptives
Fotherby, K.
American Journal of Obstetrics and Gynecology 163(6 Part 2): 2153-2159
1990
ISSN/ISBN: 0002-9378 PMID: 2256524 DOI: 10.1016/0002-9378(90)90556-mDocument Number: 466460
Pharmacokinetic interactions between oral contraceptives (OCs) and other drugs and nutrients may occur during absorption and extrahepatic circulation, through interference with protein binding, and during hepatic metabolism. However, the most significant locus of drug interaction is the mixed function oxidase system of the liver endoplasmic reticulum. Increased activity of the mixed function oxidase system produced by other drugs tends to reduce the half-life of elimination of sex steroids and consequently of their serum concentrations and biological effect. At the same time, OC administration generally has an inhibitory effect on the metabolism of other drugs and consequent reductions in their pharmacologic activity. The rate of drug metabolism will vary according to genetic and environmental factors such as diet, alcohol use, smoking, and pathologic conditions. Although the influence of nutrition on the absorption and bioavailability of contraceptive steroids has not yet researched adequately, high-protein diets appear to stimulate the activity of the hepatic drug-oxidizing system and increase the metabolism of other drugs. Pharmacokinetic and pharmacodynamic interactions between the estrogen and gestogen components of OCs may be synergistic or antagonistic, but no correlation has been found between the rate of metabolism of the 2 steroids as reflected in their elimination half-lives. Despite evidence that some anticonvulsant, antibiotic, and antibacterial drugs reduce the efficacy of OCs, this interaction is severe enough to lead to OC failure in less than 5% of cases. It can be postulated that women in whom drug interactions lead to contraceptive failure are fast metabolizers or have liver enzyme systems especially susceptible to induction.