CC-BY-NC-ND 4.0 · AJP Rep 2018; 08(02): e106-e112
DOI: 10.1055/s-0038-1639331
Case Report
Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

Pharmacokinetics of Hydroxyprogesterone Caproate and its Primary Metabolites during Pregnancy

Kim A. Boggess
1  University of North Carolina at Chapel Hill, Chapel Hill, North Carolina
,
Jeffrey B. Baker
2  Rosemark Women Care Specialists, Idaho Falls, Idaho
,
Amy P. Murtha
3  Duke University, Durham, North Carolina
,
Alan M. Peaceman
4  Northwestern University, Chicago, Illinois
,
Dinesh M. Shah
5  University of Wisconsin, Madison, Wisconsin
,
Sylvia L. Siegfried
6  Altus Research Inc., Lake Worth, Florida
,
Robert Birch
7  AMAG Pharmaceuticals, Waltham, Massachusetts
› Author Affiliations
Further Information

Publication History

09 October 2017

15 January 2018

Publication Date:
14 May 2018 (online)

Abstract

Objective To measure pharmacokinetics of hydroxyprogesterone caproate (OHPC) and its major metabolites throughout pregnancy.

Study Design Thirty women were prescribed OHPC for recurrent preterm birth prevention. Three cohorts of subjects had blood drawn for 7 consecutive days at one of three times: cohort 1 (n = 6) after the first dose (weeks 16–20), cohort 2 (n = 8) between weeks 24 and 28, and cohort 3 (n = 16) between weeks 32 and 36. We measured serum trough levels after week 1 in cohort 1 or after two consecutive weekly doses in cohorts 2 and 3. In 10 subjects, we estimated OHPC terminal half-life at 28 days after their last dose.

Results In cohorts 1, 2, and 3, the areas under curve (ng × h/mL) for OHPC were 571.4 ± 195.2, 1,269.6 ± 285.0, and 1,268.0 ± 511.6, respectively. Maximum OHPC levels (ng/mL) were 5.0 ± 1.5, 12.5 ± 3.9, and 12.3 ± 4.9, respectively. The areas under the curve for mono-hydroxylated metabolites were 208.5 ± 92.4, 157.1 ± 64.6, and 211.2 ± 113.1, and maximum concentrations were 1.9 ± 0.7, 1.5 ± 0.7, and 1.8 ± 1.0, respectively. Di-hydroxylated metabolite levels were significantly lower than mono-hydroxylated metabolites. Estimated terminal half-life of OHPC was 16.3 ± 3.6 days and 19.7 ± 6.2 days for the mono-hydroxylated metabolites.

Conclusion After the first injection, OHPC maximum serum level was approximately half steady-state level. Measurable metabolites of unknown activity were detected.