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.
Keywords
gestation - hydroxyprogesterone - metabolites - pharmacokinetics - pregnancy - preterm
birth
