Population pharmacokinetics of 17alpha-hydroxyprogesterone caproate in singleton gestation.
Citation: British Journal of Clinical Pharmacology. 82(4):1084-93, 2016 OctPMID: 27133963Institution: MedStar Health Research InstituteForm of publication: Journal ArticleMedline article type(s): Journal ArticleSubject headings: *Hydroxyprogesterones/pk [Pharmacokinetics] | Adult | Body Weight | Female | Fetal Blood | Humans | Hydroxyprogesterones/bl [Blood] | Models, Biological | Pregnancy | Young AdultYear: 2016ISSN:- 0306-5251
Item type | Current library | Collection | Call number | Status | Date due | Barcode |
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Journal Article | MedStar Authors Catalog | Article | 27133963 | Available | 27133963 |
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.
CONCLUSIONS: The population PK study reported here represents the initial steps in understanding and optimizing 17-OHPC therapy for preventing preterm birth.
Copyright � 2016 The British Pharmacological Society.
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.
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