TY - JOUR T1 - Metabolism of 17α-Hydroxyprogesterone Caproate, an Agent for Preventing Preterm Birth, by Fetal Hepatocytes JF - Drug Metabolism and Disposition JO - Drug Metab Dispos SP - 723 LP - 727 DO - 10.1124/dmd.109.029918 VL - 38 IS - 5 AU - Shringi Sharma AU - Ewa C. S. Ellis AU - Kenneth Dorko AU - Shimin Zhang AU - Donald R. Mattison AU - Steve N. Caritis AU - Raman Venkataramanan AU - Stephen C. Strom Y1 - 2010/05/01 UR - http://dmd.aspetjournals.org/content/38/5/723.abstract N2 - Preterm delivery (i.e., delivery before 37 completed weeks of gestation) is a major determinant of neonatal morbidity and mortality. Until recently, no effective therapies for prevention of preterm birth existed. In a recent multicentered trial, 17α-hydroxyprogesterone caproate (17-OHPC) was shown to reduce the rate of preterm birth by 33% in a group of high-risk women. Limited pharmacologic data exist for this drug. Previous studies have shown that CYP3A is involved in the metabolism of 17-OHPC. In this study, we evaluated the metabolism of 17-OHPC in adult and fetal human hepatocytes and in expressed cytochrome P450 enzymes. 17-OHPC was metabolized by expressed CYP3A7 and by fetal hepatocytes. The metabolite profile was qualitatively different between expressed CYP3A4 and CYP3A7. Expressed CYP3A4 demonstrated a significantly higher (>10 times) capacity to metabolize 17-OHPC than CYP3A7. Based on retention times, two unique metabolites were observed in the fetal and adult hepatocyte systems along with one common metabolite. The intrinsic clearance of 17-OHPC by fetal hepatocytes was observed to be one-half of that in adults. In summary, this study demonstrates that fetal hepatocytes and, in particular, the fetal form of CYP3A (i.e., CYP3A7) can metabolize 17-OHPC. U.S. Government work not protected by U.S. copyright ER -