Skip to main content
Advertisement

Main menu

  • Home
  • Articles
    • Current Issue
    • Fast Forward
    • Latest Articles
    • Special Sections
    • Archive
  • Information
    • Instructions to Authors
    • Submit a Manuscript
    • FAQs
    • For Subscribers
    • Terms & Conditions of Use
    • Permissions
  • Editorial Board
  • Alerts
    • Alerts
    • RSS Feeds
  • Virtual Issues
  • Feedback
  • Submit
  • Other Publications
    • Drug Metabolism and Disposition
    • Journal of Pharmacology and Experimental Therapeutics
    • Molecular Pharmacology
    • Pharmacological Reviews
    • Pharmacology Research & Perspectives
    • ASPET

User menu

  • My alerts
  • Log in
  • My Cart

Search

  • Advanced search
Drug Metabolism & Disposition
  • Other Publications
    • Drug Metabolism and Disposition
    • Journal of Pharmacology and Experimental Therapeutics
    • Molecular Pharmacology
    • Pharmacological Reviews
    • Pharmacology Research & Perspectives
    • ASPET
  • My alerts
  • Log in
  • My Cart
Drug Metabolism & Disposition

Advanced Search

  • Home
  • Articles
    • Current Issue
    • Fast Forward
    • Latest Articles
    • Special Sections
    • Archive
  • Information
    • Instructions to Authors
    • Submit a Manuscript
    • FAQs
    • For Subscribers
    • Terms & Conditions of Use
    • Permissions
  • Editorial Board
  • Alerts
    • Alerts
    • RSS Feeds
  • Virtual Issues
  • Feedback
  • Submit
  • Visit dmd on Facebook
  • Follow dmd on Twitter
  • Follow ASPET on LinkedIn
Research ArticleArticle

Identification of Enzymes Involved in the Metabolism of 17α-Hydroxyprogesterone Caproate: An Effective Agent for Prevention of Preterm Birth

Shringi Sharma, Junhai Ou, Stephen Strom, Don Mattison, Steve Caritis and Raman Venkataramanan
Drug Metabolism and Disposition September 2008, 36 (9) 1896-1902; DOI: https://doi.org/10.1124/dmd.108.021444
Shringi Sharma
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Junhai Ou
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Stephen Strom
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Don Mattison
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Steve Caritis
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Raman Venkataramanan
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • Article
  • Figures & Data
  • Info & Metrics
  • eLetters
  • PDF
Loading

Abstract

Preterm delivery, that is delivery before 37 completed weeks of gestation, is the 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) reduced the rate of preterm birth by 33% in a group of high-risk women. Limited pharmacologic data exist for this drug. The recommended dose is empiric; the metabolic pathways are not well defined especially in pregnant women; and the fetal exposure has not been quantified. To define the metabolic pathways of 17-OHPC we used human liver microsomes (HLMs), fresh human hepatocytes (FHHs), and expressed enzymes. HLMs in the presence of NADPH generated three metabolites, whereas two major metabolites were observed with FHHs. Metabolism of 17-OHPC was significantly inhibited by the CYP3A4 inhibitors ketoconazole and troleandomycin in HLM and FHH. Metabolism of 17-OHPC was significantly greater in FHH treated with the CYP3A inducers, rifampin and phenobarbital. Furthermore, studies with expressed enzymes showed that 17-OHPC is metabolized exclusively by CYP3A4 and CYP3A5. The caproic acid ester was intact in the major metabolites generated, indicating that 17-OHPC is not converted to the primary progesterone metabolite, 17α-hydroxyprogesterone. In summary, this study shows that 17-OHPC is metabolized by CYP3A. Because CYP3A is involved in the oxidative metabolism of numerous commonly used drugs, 17-OHPC may be involved in clinically relevant metabolic drug interactions with coadministered CYP3A inhibitors or inducers.

Footnotes

  • This work is supported in part by National Institute of Child Health and Human Development Grant HD-047905-2.

  • Article, publication date, and citation information can be found at http://dmd.aspetjournals.org.

  • doi:10.1124/dmd.108.021444.

  • ABBREVIATIONS: 17-OHPC, 17α-hydroxyprogesterone caproate; P450, cytochrome P450; FMO, flavin-containing monooxygenase; HLM, human liver microsome; HPLC, high-performance liquid chromatography; HMM, hepatocyte maintenance medium; FHH, fresh human hepatocyte; LC/MS, liquid chromatography/mass spectrometry; MS/MS, tandem mass spectrometry.

    • Received March 13, 2008.
    • Accepted June 19, 2008.
  • The American Society for Pharmacology and Experimental Therapeutics
View Full Text

 

DMD articles become freely available 12 months after publication, and remain freely available for 5 years. 

Non-open access articles that fall outside this five year window are available only to institutional subscribers and current ASPET members, or through the article purchase feature at the bottom of the page. 

 

  • Click here for information on institutional subscriptions.
  • Click here for information on individual ASPET membership.

 

Log in using your username and password

Forgot your user name or password?

Purchase access

You may purchase access to this article. This will require you to create an account if you don't already have one.
PreviousNext
Back to top

In this issue

Drug Metabolism and Disposition: 36 (9)
Drug Metabolism and Disposition
Vol. 36, Issue 9
1 Sep 2008
  • Table of Contents
  • Table of Contents (PDF)
  • About the Cover
  • Index by author
  • Back Matter (PDF)
  • Editorial Board (PDF)
  • Front Matter (PDF)
Download PDF
Article Alerts
Sign In to Email Alerts with your Email Address
Email Article

Thank you for sharing this Drug Metabolism & Disposition article.

NOTE: We request your email address only to inform the recipient that it was you who recommended this article, and that it is not junk mail. We do not retain these email addresses.

Enter multiple addresses on separate lines or separate them with commas.
Identification of Enzymes Involved in the Metabolism of 17α-Hydroxyprogesterone Caproate: An Effective Agent for Prevention of Preterm Birth
(Your Name) has forwarded a page to you from Drug Metabolism & Disposition
(Your Name) thought you would be interested in this article in Drug Metabolism & Disposition.
CAPTCHA
This question is for testing whether or not you are a human visitor and to prevent automated spam submissions.
Citation Tools
Research ArticleArticle

Identification of Enzymes Involved in the Metabolism of 17α-Hydroxyprogesterone Caproate: An Effective Agent for Prevention of Preterm Birth

Shringi Sharma, Junhai Ou, Stephen Strom, Don Mattison, Steve Caritis and Raman Venkataramanan
Drug Metabolism and Disposition September 1, 2008, 36 (9) 1896-1902; DOI: https://doi.org/10.1124/dmd.108.021444

Citation Manager Formats

  • BibTeX
  • Bookends
  • EasyBib
  • EndNote (tagged)
  • EndNote 8 (xml)
  • Medlars
  • Mendeley
  • Papers
  • RefWorks Tagged
  • Ref Manager
  • RIS
  • Zotero

Share
Research ArticleArticle

Identification of Enzymes Involved in the Metabolism of 17α-Hydroxyprogesterone Caproate: An Effective Agent for Prevention of Preterm Birth

Shringi Sharma, Junhai Ou, Stephen Strom, Don Mattison, Steve Caritis and Raman Venkataramanan
Drug Metabolism and Disposition September 1, 2008, 36 (9) 1896-1902; DOI: https://doi.org/10.1124/dmd.108.021444
Reddit logo Twitter logo Facebook logo Mendeley logo
  • Tweet Widget
  • Facebook Like
  • Google Plus One

Jump to section

  • Article
    • Abstract
    • Materials and Methods
    • Results
    • Discussion
    • Acknowledgments
    • Footnotes
    • References
  • Figures & Data
  • Info & Metrics
  • eLetters
  • PDF

Related Articles

Cited By...

More in this TOC Section

  • A PBPK model for CBD in adults and children
  • Olanzapine Glucuronidation in Humanized Mice
  • rs2242480 Regulates the Expression of CYP3A4 and CYP3A5
Show more Articles

Similar Articles

Advertisement
  • Home
  • Alerts
Facebook   Twitter   LinkedIn   RSS

Navigate

  • Current Issue
  • Fast Forward by date
  • Fast Forward by section
  • Latest Articles
  • Archive
  • Search for Articles
  • Feedback
  • ASPET

More Information

  • About DMD
  • Editorial Board
  • Instructions to Authors
  • Submit a Manuscript
  • Customized Alerts
  • RSS Feeds
  • Subscriptions
  • Permissions
  • Terms & Conditions of Use

ASPET's Other Journals

  • Journal of Pharmacology and Experimental Therapeutics
  • Molecular Pharmacology
  • Pharmacological Reviews
  • Pharmacology Research & Perspectives
ISSN 1521-009X (Online)

Copyright © 2023 by the American Society for Pharmacology and Experimental Therapeutics