Population pharmacokinetics of 17α-hydroxyprogesterone caproate in singleton gestation

Shringi Sharma, Steve Caritis, Gary Hankins, Menachem Miodovnik, Mary F. Hebert, Don Mattison, Raman Venkataramanan

Research output: Contribution to journalArticle

3 Citations (Scopus)

Abstract

Aims: 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. 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.

Original languageEnglish (US)
Pages (from-to)1084-1093
Number of pages10
JournalBritish Journal of Clinical Pharmacology
DOIs
StatePublished - Oct 1 2016

Fingerprint

17-alpha-Hydroxyprogesterone
Pharmacokinetics
Pregnancy
Mothers
Premature Birth
Population
Castor Oil
Intrinsic Factor
Intramuscular Injections
Fetal Blood
17-alpha-hydroxy-progesterone caproate
Body Weight
Injections
Therapeutics

Keywords

  • 17α-hydroxyprogesterone caproate
  • population pharmacokinetics
  • preterm birth

ASJC Scopus subject areas

  • Pharmacology
  • Pharmacology (medical)

Cite this

Sharma, S., Caritis, S., Hankins, G., Miodovnik, M., Hebert, M. F., Mattison, D., & Venkataramanan, R. (2016). Population pharmacokinetics of 17α-hydroxyprogesterone caproate in singleton gestation. British Journal of Clinical Pharmacology, 1084-1093. https://doi.org/10.1111/bcp.12990

Population pharmacokinetics of 17α-hydroxyprogesterone caproate in singleton gestation. / Sharma, Shringi; Caritis, Steve; Hankins, Gary; Miodovnik, Menachem; Hebert, Mary F.; Mattison, Don; Venkataramanan, Raman.

In: British Journal of Clinical Pharmacology, 01.10.2016, p. 1084-1093.

Research output: Contribution to journalArticle

Sharma, S, Caritis, S, Hankins, G, Miodovnik, M, Hebert, MF, Mattison, D & Venkataramanan, R 2016, 'Population pharmacokinetics of 17α-hydroxyprogesterone caproate in singleton gestation', British Journal of Clinical Pharmacology, pp. 1084-1093. https://doi.org/10.1111/bcp.12990
Sharma, Shringi ; Caritis, Steve ; Hankins, Gary ; Miodovnik, Menachem ; Hebert, Mary F. ; Mattison, Don ; Venkataramanan, Raman. / Population pharmacokinetics of 17α-hydroxyprogesterone caproate in singleton gestation. In: British Journal of Clinical Pharmacology. 2016 ; pp. 1084-1093.
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