Abstract

PIP: This document attempts to fill in some gaps with regard to the clinical pharmacology of oral contraceptives (OCs). The total dose level cannot be reduced much further without impairing the contraceptive efficacy of the drug. Plasma concentration of steroids varies widely from individual to individual. The bioavailability of norethisterone and ethinyl estradiol (EE) is incomplete when drugs are given orally as opposed to intravenously. Reduced norethisterone bioavailability is due to a 1st pass effect; drugs may undergo 1st pass elimination either in the gut wall or in the liver. With EE, the values of EE sulphate were higher when EE was administered orally than when it was given intravenously. This suggests that after oral dosing, a significant part of the 1st pass effect is due to sulphate conjugation in the gut wall. Norethisterone and levonorgestrel are extensively bound to albumin and sex hormone binding globulin in plasma. This binding capacity can be enhanced by EE and drugs such as phenobarbitone. EE is also bound to albumin. While OC therapy may interfere with the activity of the other drug treatment given at the same time, this is not clinically of major importance. OCs may diminish the effects of anticoagulants, of oral hypoglycemic drugs, or of antihypertensive drugs. Likewise, the effect of OCs may be altered by the simultaneous administration of other drugs. It is also apparent that the effect of OCs may be enhanced by vitamin C. Rifampicin, a potent inducer of hepatic microsomal drug metabolizing enzymes, does diminish the efficacy of OCs. Anticonvulsants and antibiotics are also in the same category. The interaction between OCs and antibiotics is probably the most controversial of all. There have been reports in the literature about women who have become pregnant while taking OCs and antibiotics. It is likely that the majority of women are not at risk of contraceptive failure when using a broad spectrum antibiotic at the same time as the OC.