Citation: British Journal of Clinical Pharmacology. 82(4):1084-93, 2016 Oct.Journal: British journal of clinical pharmacology.Published: 2016ISSN: 0306-5251.Full author list: Sharma S; Caritis S; Hankins G; Miodovnik M; Hebert MF; Mattison D; Venkataramanan R.UI/PMID: 27133963.Subject(s): Adult | Body Weight | Female | Fetal Blood | Humans | Hydroxyprogesterones/bl [Blood] | *Hydroxyprogesterones/pk [Pharmacokinetics] | Models, Biological | Pregnancy | Young AdultInstitution(s): MedStar Health Research InstituteActivity type: Journal Article.Medline article type(s): Journal ArticleDigital Object Identifier: https://dx.doi.org/10.1111/bcp.12990 (Click here)Abbreviated citation: Br J Clin Pharmacol. 82(4):1084-93, 2016 Oct.Abstract: AIMS: 17alpha-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.Abstract: 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() ).Abstract: 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.Abstract: CONCLUSIONS: The population PK study reported here represents the initial steps in understanding and optimizing 17-OHPC therapy for preventing preterm birth.Abstract: Copyright � 2016 The British Pharmacological Society.