Metabolism of 17alpha-hydroxyprogesterone caproate, an agent for preventing preterm birth, by fetal hepatocytes.

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Sharma S, Ellis EC, Dorko K, Zhang S, Mattison DR, Caritis SN, Venkataramanan R, Strom SC

Metabolism of 17alpha-hydroxyprogesterone caproate, an agent for preventing preterm birth, by fetal hepatocytes.

Drug Metab Dispos. 2010 May;38(5):723-7. doi: 10.1124/dmd.109.029918. Epub 2010 Jan 22.

PubMed ID

20097724 [ View in PubMed

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Abstract

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, 17alpha-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.

DrugBank Data that Cites this Article

Drug Enzymes

Drug	Enzyme	Kind	Organism	Pharmacological Action	Actions
Progesterone	Cytochrome P450 3A7	Protein	Humans	Unknown	Substrate Inhibitor	Details