Effect of Hormonal Contraceptives on the Pharmacokinetics of Trovafloxacin in Women

Abstract

Objective

To study the impact of hormone-based contraceptives on the pharmacokinetics of oral trovafloxacin.

Methods

20 healthy premenopausal women, 10 taking hormonal contraception and 10 using non-hormonal methods, received a single 200mg oral dose of trovafloxacin. 16 plasma samples were collected prior to and for 24 hours after drug administration.

Results

Despite the high incidence of central nervous system- and gastrointestinal-related adverse events (≥80% in hormonal and non-hormonal groups), all participants completed the study. Results demonstrated that women using hormonal methods of contraception had significantly lower peak plasma concentrations (1.92 vs 2.27 mg/L, p = 0.03) than those using non-hormonal methods. They also demonstrated significantly higher clearance rates (9.96 vs 7.62 L/h, p < 0.004) and lower exposures (AUC) [20.8 vs 26.7 mg/L·h, p < 0.004] to the drug.

Conclusions

Based on previous studies, it is thought that the changes in trovafloxacin pharmacokinetics are secondary to induction or competition at cytochrome P-450 2C19 with the progestin components and/or an increase in phase II conjugation reactions by the estrogen components. However, a hormone-induced change in bioavailability cannot be ruled out as being responsible for the changes reported. The clinical significance of this interaction needs to be studied more fully. However, based on presently accepted pharmacodynamic drug administration parameters, the clinical effectiveness of trovafloxacin when used in premenopausal women receiving hormone-based contraceptives may be less than optimal, especially against pathogens with borderline sensitivities.