Pharmacokinetics of Hydroxyprogesterone Caproate and its Primary Metabolites during Pregnancy

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.