title: Population pharmacokinetics of 17α-hydroxyprogesterone caproate in singleton gestation.
abstract: 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.
  
  
  
  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(®) ).
  
  
  
  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.
  
  
  
  The population PK study reported here represents the initial steps in understanding and optimizing 17-OHPC therapy for preventing preterm birth.
authors.affiliation: Department of Pharmaceutical Sciences, School of Pharmacy, University of Pittsburgh, Pittsburgh, PA, USA. shringisharma@yahoo.com.
authors.forename: Shringi
authors.initials: S
authors.lastname: Sharma
authors.affiliation: Departments of Obstetrics, Gynecology and Reproductive Sciences, Magee-Women's Hospital, University of Pittsburgh Medical Center, Pittsburgh, PA, USA.
authors.forename: Steve
authors.initials: S
authors.lastname: Caritis
authors.affiliation: Department of Obstetrics and Gynecology, University of Texas Medical Branch, Galveston, TX, USA.
authors.forename: Gary
authors.initials: G
authors.lastname: Hankins
authors.affiliation: Medstar Health Research Institute, Hyatsville, MD, USA.|Georgetown-Howards University Center for Clinical and Translational Science, Washington, DC, USA.
authors.forename: Menachem
authors.initials: M
authors.lastname: Miodovnik
authors.affiliation: Department of Pharmacy and Obstetrics & Gynecology, University of Washington, Seattle, WA, USA.
authors.forename: Mary F
authors.initials: MF
authors.lastname: Hebert
authors.affiliation: McLaughlin Centre for Population Health Risk Assessment, University of Ottawa, and Risk Sciences International, Ottawa, ON, Canada.
authors.forename: Don
authors.initials: D
authors.lastname: Mattison
authors.affiliation: Department of Pharmaceutical Sciences, School of Pharmacy, University of Pittsburgh, Pittsburgh, PA, USA.
authors.forename: Raman
authors.initials: R
authors.lastname: Venkataramanan
mesh_terms: D000077713:17 alpha-Hydroxyprogesterone Caproate; D000328:Adult; D001835:Body Weight; D005260:Female; D005312:Fetal Blood; D006801:Humans; D006908:Hydroxyprogesterones / Q000097:blood / Q000493:pharmacokinetics*; D008954:Models, Biological; D011247:Pregnancy; D055815:Young Adult
chemical_list: D006908:Hydroxyprogesterones; D000077713:17 alpha-Hydroxyprogesterone Caproate
keywords: 17α-hydroxyprogesterone caproate; population pharmacokinetics; preterm birth