Mouse Anti-17 Alpha-hydroxyprogesterone Hybridoma [PIQ8E8.3.4]

Prevention of preterm delivery is a major desiderate in contemporary obstetrics and a societal necessity. The means to achieve this goal remain elusive. Progesterone has been used in an attempt to prevent preterm delivery since the 1970s, but the evidence initially accumulated was fraught by mixed results and was based on mostly underpowered studies with variable eligibility criteria, including history of spontaneous abortion as an indication for treatment. More recent randomized controlled clinical trials restimulated the interest in progesterone supplementation, suggesting that progesterone may favorably influence the rate of preterm delivery. Preterm delivery is a complex disorder and consequently it is unlikely that one generalized prevention strategy will be effective in all patients. Further, an additional impediment in accepting progesterone as the "magic bullet" in the prevention of preterm delivery is that its mechanism of action is not fully understood and the optimal formulations, route of administration, and dose have yet to be established. We have concerned ourselves in this review with the most recent status of 17 alpha-hydroxyprogesterone caproate (17OH-PC) supplementation for prevention of preterm delivery. Our intention is to emphasize the efficacy, safety, and patient acceptability of this intervention, based on a comprehensive and unbiased review of the available literature. Currently there are insufficient data to suggest that 17OH-PC is superior or inferior to natural progesterone. Based on available evidence, we suggest a differential approach giving preferential consideration to either 17OH-PC or other progestins based on obstetric history and cervical surveillance. Progestin therapy for risk factors other than a history of preterm birth and/or a short cervix in the current pregnancy is not currently supported by the published evidence. The experience to date with 17OH-PC indicates that there are population subgroups that may be harmed by administration of 17OH-PC. Therefore, extending the use of 17OH-PC to unstudied populations or for indications that are not evidence-based is inadvisable outside of a research protocol.

Aims17-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. MethodsSixty-one women with singleton pregnancies participated in this trial. Subjects received weekly intramuscular injections of 250mg 17-OHPC in 1ml 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 (R)). ResultsThe 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 (V-maternal/F). The final population mean estimates were: CL/F 1797l/d, V-maternal/F 32610l and mother to cord rate constant 0.005day(-1). This report describes for the first time the population PK of 17-OHPC in singleton pregnancy. ConclusionsThe population PK study reported here represents the initial steps in understanding and optimizing 17-OHPC therapy for preventing preterm birth.