Establishing a Quantitative Framework for Combined Oral Contraceptives: Evaluating the Impact of Drug-Drug Interactions on Exposure and Clinical (Surrogate) Efficacy Endpoints.

ABSTRACT: According to the FDA Guidance for Industry on Clinical Drug Interaction (DDI) Studies with Combined Oral Contraceptives (COCs), sponsors are expected to conduct dedicated clinical DDI studies if in vitro findings suggest weak or moderate CYP3A induction, while concomitant use of COCs with strong inducers should be avoided. The guidance further suggests that a negative DDI result for drospirenone (DRSP) may be extrapolated to other progestins that are less sensitive to CYP3A modulation, such as levonorgestrel (LNG). This approach assumes that DDI-mediated changes in exposure directly translate into clinical efficacy across progestins. To evaluate the validity of this assumption, we established a quantitative link between dose, exposure, and response (Pearl Index [PI] and ovulation rate [OR]

SUBMITTER: Chun D 

PROVIDER: S-EPMC12649304 | biostudies-literature | 2025 Dec

REPOSITORIES: biostudies-literature