Effect of oral contraceptives on triazolam, temazepam, alprazolam, and lorazepam kinetics

Abstract

The effects of low-dose estrogen oral contraceptives (OC) on the elimination of the oxidized benzodiazepines triazolam (TRZ) [a hypnotic] and alprazolam (ALP) [an anxiolytic] and the conjugated benzodiazepines temazepam (TMZ) [an antiinsomnia drug] and lorazepam (LOR) [an anxiolytic] were studied in 2 parallel crossover studies of 20 women each. Women taking OC steroids containing low doses of estrogen and women matched for age, weight, and cigarette smoking received single oral doses of TRZ (0.5 mg) and TMZ (30 mg) or ALP (1 mg) and LOR (2 mg). Kinetics were determined as plasma concentrations during 48 h after dosing. OC inhibited the metabolism of ALP. The AUC [area under the curve] increased and the elimination rate constant was greater in users of OC. For TRZ, which has an intermediate extraction ratio, the AUC was increased by OC but not significantly so. OC decreased the AUC for TMZ and the elimination rate constants for LOR and TMZ. The AUC of LOR was not affected by OC. Low-dose estrogen OC may therefore inhibit the metabolism of some oxidized benzodiazepines and accelerate the metabolism of some conjugated benzodiazepines.