Metabolism of 17α-hydroxyprogesterone caproate by hepatic and placental microsomes of human and baboons

Ru Yan, Tatiana Nanovskaya, Olga L. Zharikova, Donald R. Mattison, Gary Hankins, Mahmoud Ahmed

Research output: Contribution to journalArticle

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Abstract

Recent data from our laboratory revealed the formation of an unknown metabolite of 17 hydroxyprogesterone caproate (17-HPC), used for treatment of preterm deliveries, during its perfusion across the dually perfused human placental lobule. Previously, we demonstrated that the drug is not hydrolyzed, neither in vivo nor in vitro, to progesterone and caproate. Therefore, the hypothesis for this investigation is that 17-HPC is actively metabolized by human and baboon (Papio cynocephalus) hepatic and placental microsomes. Baboon hepatic and placental microsomes were investigated to validate the nonhuman primate as an animal model for drug use during pregnancy. Data presented here indicate that human and baboon hepatic microsomes formed several mono-, di-, and tri-hydroxylated derivatives of 17-HPC. However, microsomes of human and baboon placentas metabolized 17-HPC to its mono-hydroxylated derivatives only in quantities that were a fraction of those formed by their respective livers, except for two metabolites (M16′ and M17′) that are unique for placenta and contributed to 25% and 75% of the total metabolites formed by human and baboon, respectively. The amounts of metabolites formed, relative to each other, by human and baboon microsomes were different suggesting that the affinity of 17-HPC to CYP enzymes and their activity could be species-dependent.

Original languageEnglish (US)
Pages (from-to)1848-1857
Number of pages10
JournalBiochemical Pharmacology
Volume75
Issue number9
DOIs
StatePublished - May 1 2008

Fingerprint

17-alpha-Hydroxyprogesterone
Papio
Microsomes
Metabolism
Metabolites
Liver
Placenta
Derivatives
Papio cynocephalus
Pharmaceutical Preparations
Progesterone
Animals
Primates
17-alpha-hydroxy-progesterone caproate
Animal Models
Perfusion
Enzymes
Pregnancy

Keywords

  • 17α-Hydroxyprogesterone caproate
  • Baboon liver
  • Baboon placenta
  • Human liver
  • Human placenta
  • Metabolism
  • Microsomes
  • Preterm delivery

ASJC Scopus subject areas

  • Pharmacology

Cite this

Metabolism of 17α-hydroxyprogesterone caproate by hepatic and placental microsomes of human and baboons. / Yan, Ru; Nanovskaya, Tatiana; Zharikova, Olga L.; Mattison, Donald R.; Hankins, Gary; Ahmed, Mahmoud.

In: Biochemical Pharmacology, Vol. 75, No. 9, 01.05.2008, p. 1848-1857.

Research output: Contribution to journalArticle

Yan, Ru ; Nanovskaya, Tatiana ; Zharikova, Olga L. ; Mattison, Donald R. ; Hankins, Gary ; Ahmed, Mahmoud. / Metabolism of 17α-hydroxyprogesterone caproate by hepatic and placental microsomes of human and baboons. In: Biochemical Pharmacology. 2008 ; Vol. 75, No. 9. pp. 1848-1857.
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