title: Route of administration and formulation dependent pharmacokinetics of 17-hydroxyprogesterone caproate in rats.
abstract: 1. Weekly intramuscular injections of (250 mg/week) of 17-hydroxyprogesterone caproate (17-OHPC) are the only treatment option for prevention of preterm birth in women with a prior history of preterm delivery. 2. The objective of the current study was to evaluate the use of an alternate formulation and the feasibility of an alternate route of administration of this agent. 17-OHPC was administered to adult female SD rats, as marketed oily formulation intramuscularly, or as a solution IV, IM, or PO. 3. Plasma concentrations of 17-OHPC were measured by LC-MS-MS and pharmacokinetic parameters were calculated by non-compartmental analysis, using WinNonLin (Certara, St. Louis, MO). 4. After IV or IM administration as a solution, the mean half-life of 17-OHPC was around 11 h. The bioavailability was nearly 100% after IM administration, but was very low (<3%) after PO administration of a solution dosage form. 5. Intramuscular injection of the oily formulation resulted in low levels of 17-OHPC that were sustained for a prolonged time period with a projected bioavailability close to 100%. 6. The pharmacokinetics of 17-OHPC is dependent on the formulation and the route of administration. 7. The low bioavailability after oral administration indicates that oral administration of 17-OHPC may not be feasible with simple formulations of this drug.
authors.affiliation: a Department of Pharmaceutical Sciences , School of Pharmacy, University of Pittsburgh , Pittsburgh , PA , USA .
authors.forename: Imam H
authors.initials: IH
authors.lastname: Shaik
authors.affiliation: a Department of Pharmaceutical Sciences , School of Pharmacy, University of Pittsburgh , Pittsburgh , PA , USA .|b Department of Obstetrics , Gynecology and Reproductive Sciences, School of Medicine, Magee-Women's Hospital , Pittsburgh , PA , USA .
authors.forename: Jaime R
authors.initials: JR
authors.lastname: Bastian
authors.affiliation: a Department of Pharmaceutical Sciences , School of Pharmacy, University of Pittsburgh , Pittsburgh , PA , USA .
authors.forename: Yang
authors.initials: Y
authors.lastname: Zhao
authors.affiliation: b Department of Obstetrics , Gynecology and Reproductive Sciences, School of Medicine, Magee-Women's Hospital , Pittsburgh , PA , USA .|c Magee-Women's Research Institute , Pittsburgh , PA , USA , and.
authors.forename: Steve N
authors.initials: SN
authors.lastname: Caritis
authors.affiliation: a Department of Pharmaceutical Sciences , School of Pharmacy, University of Pittsburgh , Pittsburgh , PA , USA .|c Magee-Women's Research Institute , Pittsburgh , PA , USA , and.|d Department of Pathology , School of Medicine, University of Pittsburgh , Pittsburgh , PA , USA.
authors.forename: Raman
authors.initials: R
authors.lastname: Venkataramanan
mesh_terms: D000077713:17 alpha-Hydroxyprogesterone Caproate; D000284:Administration, Oral; D000818:Animals; D001682:Biological Availability; D002853:Chromatography, Liquid; D004305:Dose-Response Relationship, Drug; D005240:Feasibility Studies; D005260:Female; D006207:Half-Life; D006908:Hydroxyprogesterones / Q000008:administration & dosage* / Q000493:pharmacokinetics*; D007273:Injections, Intramuscular; D051381:Rats; D017207:Rats, Sprague-Dawley; D053719:Tandem Mass Spectrometry
chemical_list: D006908:Hydroxyprogesterones; D000077713:17 alpha-Hydroxyprogesterone Caproate
keywords: 17-OHPC; Absorption; CYP 3A 4/5 metabolism; LC-MS/MS; jugular vein cannulation; pharmacokinetics; preterm birth