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Pharmacokinetics of a Controlled-Release Misoprostol Vaginal Insert at Term

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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 μg (7 at 200 μg) 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-μg 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 · 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. (J Soc Gynecol Investig 2006;13:112-7) Copyright © 2006 by the Society for Gynecologic Investigation.

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Authors and Affiliations

  1. Department of Obstetrics and Gynecology, University of New Mexico, School of Medicine, Albuquerque, NM, USA

    William F. Rayburn MD, Barbara L. Powers MSN, PhD, Terry F. Plasse MD, Denis Carr MSc, MRSC, CChem & Mike Di Spirito MSc

  2. Cytokine PharmaSciences Inc, Walnut Hill Plaza, 150 S. Warner Rd., Suite 420, King of Prussia, PA, 19406, USA

    William F. Rayburn MD, Barbara L. Powers MSN, PhD, Terry F. Plasse MD, Denis Carr MSc, MRSC, CChem & Mike Di Spirito MSc

  3. Controlled Therapeutics, East Kilbride, Scotland

    William F. Rayburn MD, Barbara L. Powers MSN, PhD, Terry F. Plasse MD, Denis Carr MSc, MRSC, CChem & Mike Di Spirito MSc

  4. MDS Pharma Services, Montreal, Quebec, Canada

    William F. Rayburn MD, Barbara L. Powers MSN, PhD, Terry F. Plasse MD, Denis Carr MSc, MRSC, CChem & Mike Di Spirito MSc

Authors
  1. William F. Rayburn MD
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  2. Barbara L. Powers MSN, PhD
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  3. Terry F. Plasse MD
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  4. Denis Carr MSc, MRSC, CChem
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  5. Mike Di Spirito MSc
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Corresponding author

Correspondence to Barbara L. Powers MSN, PhD.

Additional information

Supported by Controlled Therapeutics, East Kilbride, Scotland.

Presented at the 52nd Annual Meeting of the Society for Gynecologic Investigation, Los Angeles, CA, March 25, 2005 (abstr 192).

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Rayburn, W.F., Powers, B.L., Plasse, T.F. et al. Pharmacokinetics of a Controlled-Release Misoprostol Vaginal Insert at Term. Reprod. Sci. 13, 112–117 (2006). https://doi.org/10.1016/j.jsgi.2005.10.004

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