Pharmacokinetics of a controlled-release misoprostol vaginal insert at term

Abstract

Objective: The objective of this investigation was to report the pharmacokinetic properties of misoprostol administered intravaginally to women at term via a controlled-release hydrogel polymer insert.

Methods: This open-label, dose escalation trial consisted of 31 nulliparous women at term who were treated intravaginally in cohorts of six with inserts containing reservoirs from 25 through 300 microg (7 at 200 microg) of misoprostol. Inserts remained intravaginally until the patient went into labor, developed adverse events, or completed 24 hours of treatment. Complete data about residual drug in the inserts and plasma concentrations of misoprostol acid were gathered for 27 and 25 patients, respectively.

Results: Misoprostol was released at a constant rate (5.1% total dose per hour) with the amount absorbed being directly proportional to the dose reservoir. For the 25-, 50-, 100-, 200-, and 300-microg reservoir doses, the maximum median plasma concentrations were 6.4, 11.3, 21.7, 40.8, and 74.2 pg/mL, respectively, and the area under the curve until drug removal was 39, 117, 223, 269, and 477 pg x h/mL. Regardless of dose, the peak plasma concentration occurred at approximately 7 hours after insertion and the elimination half-life of the misoprostol acid was 0.55 hours (95% confidence interval, 0.36 to 1.32 hours).

Conclusions: Misoprostol is released from the vaginal insert in a controlled manner and is eliminated rapidly after removal. Pharmacokinetic parameters are proportional to the reservoir dose.