A pharmacokinetic study comparing a low-dose estrogen contraceptive transdermal system with an oral contraceptive tablet in healthy adult females.

Abstract

Background: This study evaluated the pharmacokinetics (PK) of a once-weekly low-dose estrogen contraceptive transdermal system (TDS) and a once-daily combined oral contraceptive (COC) in healthy women.

Research design and methods: In this Phase 1 study, 24 healthy women aged 18-35 years were randomized to a crossover sequence of three consecutive 168-h applications of the norelgestromin (NGMN; drug load, 4.86 mg)/ethinyl estradiol (EE; drug load, 0.264 mg) TDS to the abdomen (Treatment A) or buttock (Treatment B), followed by once-daily COC (drug load 0.18 mg norgestimate/0.025 mg EE) for 7 days (Treatment C). Plasma NGMN and EE concentrations were assessed using PK parameters. Application-site irritation, residual patch analysis, and safety were also evaluated.

Results: Variability in NGMN and EE exposure was lower for Treatments A and B versus Treatment C (AUC_τ,ss: NGMN, 38.4% and 31.7% versus 47.0%; EE, 49.3% and 35.4% versus 51.2%) with comparable/lower C_{p, ss(max)} variability. EE C_{p, ss(max).} Normalized exposure were lower with the NGMN/EE TDS. No serious adverse events occurred. Residual patch analysis indicated delivery of ~200 µg/day NGMN and 19 µg/day EE.

Conclusions: The NGMN/EE TDS demonstrated lower PK variability, EE peak concentrations and normalized EE exposure than the COC. No new safety signals were reported.