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Population pharmacokinetics of 17?-hydroxyprogesterone caproate in singleton gestation.

ABSTRACT: AIMS:17?-hydroxyprogesterone caproate (17-OHPC) reduces the rate of preterm birth in women with a prior preterm birth. Limited data exist on the pharmacokinetics (PK) of 17-OHPC or the plasma concentrations achieved during therapy. In this study, we evaluated the population PK of 17-OHPC in pregnant subjects with singleton gestation and also evaluated intrinsic and extrinsic factors that may potentially affect 17-OHPC PK in this patient population. METHODS:Sixty-one women with singleton pregnancies participated in this trial. Subjects received weekly intramuscular injections of 250 mg 17-OHPC in 1 ml castor oil from the time of enrolment (16 0/7 weeks - 20 6/7 weeks) up to 35 weeks gestation or until delivery. Blood samples were obtained between 24 and 28 weeks, between 32 and 35 weeks and over a 28-day period beyond the last injection. Maternal and/or cord blood were obtained at delivery. Data analysis was performed by nonlinear mixed effects modelling (NONMEM(®) ). RESULTS:The 17-OHPC PK were best described by a model with one maternal compartment and one fetal compartment, with first-order absorption and elimination from the maternal compartment. Maternal body weight was a significant covariate for both clearance (CL/F) and volume of distribution (Vmaternal /F). The final population mean estimates were: CL/F 1797 l/d, Vmaternal /F 32 610 l and mother to cord rate constant 0.005 day(-1) . This report describes for the first time the population PK of 17-OHPC in singleton pregnancy. CONCLUSIONS:The population PK study reported here represents the initial steps in understanding and optimizing 17-OHPC therapy for preventing preterm birth.

SUBMITTER: Sharma S

PROVIDER: S-EPMC5137834 | biostudies-literature | 2016 Oct

REPOSITORIES: biostudies-literature

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Population pharmacokinetics of 17α-hydroxyprogesterone caproate in singleton gestation.

Sharma Shringi S Caritis Steve S Hankins Gary G Miodovnik Menachem M Hebert Mary F MF Mattison Don D Venkataramanan Raman R

British journal of clinical pharmacology 20160713 4

<h4>Aims</h4>17α-hydroxyprogesterone caproate (17-OHPC) reduces the rate of preterm birth in women with a prior preterm birth. Limited data exist on the pharmacokinetics (PK) of 17-OHPC or the plasma concentrations achieved during therapy. In this study, we evaluated the population PK of 17-OHPC in pregnant subjects with singleton gestation and also evaluated intrinsic and extrinsic factors that may potentially affect 17-OHPC PK in this patient population.<h4>Methods</h4>Sixty-one women with sin ...[more]

PMID: 27133963

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Project description:ObjectiveTo evaluate whether 17α-hydroxyprogesterone caproate use in preventing preterm birth increases the risk of gestational diabetes mellitus (GDM).Data sourcesElectronic databases (MEDLINE, Scopus, ClinicalTrials.gov, PROSPERO, EMBASE, Scielo and the Cochrane Central Register of Controlled Trials) were searched for studies published before October 2018. Keywords included "gestational diabetes," "preterm birth," "pregnancy," and "17-hydroxyprogesterone caproate."Methods of study selectionStudies comparing 17α-hydroxyprogesterone caproate with unexposed control groups in women with singleton gestation and a history of a prior spontaneous preterm birth were included. The primary outcome was the development of GDM. Secondary outcomes included abnormal 1-hour, 50-g glucose screen results and mean venous blood glucose levels. Summary estimates were reported as mean differences and 95% CI for continuous variables or relative risk (RR) with 95% CI for dichotomous outcomes. Meta-analysis was performed using the random effects model of DerSimonian and Laird.Tabulation, integration and resultsSix studies, four of which were cohort studies, met inclusion criteria and were included in the final meta-analysis. Of the 5,053 women, 1,538 (30.4%) received 17α-hydroxyprogesterone caproate and 3,515 (69.6%) were in unexposed control groups. The overall rate of GDM in women exposed to 17α-hydroxyprogesterone caproate was 10.9% vs 6.1% in women who were not exposed (RR 1.77, 95% CI 1.22-2.55). After exclusion of the cohort studies, the summary estimate of effect was nonsignificant among women who had been randomly allocated to 17α-hydroxyprogesterone caproate (RR 1.21, 95% CI 0.63-2.36).ConclusionWomen with singleton gestations receiving weekly 17α-hydroxyprogesterone caproate for recurrent preterm birth prevention had a significantly higher incidence of abnormal glucose test results and GDM compared with those in unexposed control groups, a finding that did not hold among women who had been randomly allocated to 17α-hydroxyprogesterone caproate.Systematic review registrationPROSPERO, CRD42016041694.

Dataset Information

Population pharmacokinetics of 17?-hydroxyprogesterone caproate in singleton gestation.

Publications

Population pharmacokinetics of 17α-hydroxyprogesterone caproate in singleton gestation.

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