Impact of higher dose on pharmacokinetics of 17-alpha hydroxyl progesterone caproate (17OHPC) in obese women

Preterm birth (PTB) continues to be the leading cause of neonatal morbidity/mortality; 17OHPC may reduce PTB. Previous studies suggest higher dosing may be needed for obese patients. We sought to determine if 500mg weekly doses of 17OHPC will increase maternal plasma levels in obese (BMI >30 kg/m2) patients compared to 250 mg dose (Standard); and the impact on gestational age (GA) at delivery. Prospective 3-arm study of women with singleton pregnancies and a prior spontaneous PTB. Non-obese women (BMI 18-29.9 kg/m2) received standard weekly 17OHPC dose (Group 1). Obese women were randomized (1:1) to standard (Group2) or higher dose (500 mg, Group 3). Maternal blood was drawn at enrollment, 20–22, 27–29 and 34–36 weeks gestation and immediately before the weekly injection to obtain trough 17-OHPC levels. Outcome measures were: mean trough, mean plasma, and average peak concentrations of 17-OHPC in the 3 groups and GA at delivery. Kruskal Wallis or Wilcoxon rank sum test and a mixed model with repeated measures were used to compare levels of 17OHPC between the groups. The study was stopped after 44 (69.8%) intended 63 subjects were enrolled due to futility in recruiting women with BMI >30. Complete data (all 4 time periods) were available for 17/19 group 1, 8/16 in group 2 and 5/9 in group 3. Demographic characteristics among the 3 groups including maternal age, race, number of prior PTB, GA at blood draws were similar. GA at delivery were: 36.7 (±2.6), 38.4 (±=1.4) and 32.2 (±5.5) weeks in groups 1, 2 and 3, respectively; p=0.0049. Significant differences in 17OHPC concentrations were seen at the second draw (27-29 weeks) between the groups (p=0.0117). Mixed models showed 17 OHPC concentration was significantly different between groups, with the highest in the 500 mg group (p< 0.004). There was no significant change over GA (p=0.1571) Figs. The use of 500mg weekly dose of 17OHPC resulted in higher maternal plasma levels in obese women but did not prolong GA. Larger studies focused on optimal and effective dosing of progesterone in obese women are needed.View Large Image Figure ViewerDownload Hi-res image Download (PPT)