Skip to main content
padlock icon - secure page this page is secure

Open Access Inhibitory potential of chlormadinone acetate (CMA) on five important UDP-glucuronosyltransferases in human liver

Download Article:
(PDF 371.7 kb)
Chlormadinone acetate (CMA), a derivative of 17-a-hydroxyprogesterone, has been widely used as an orally effective progestogen in hormone replacement therapy (HRT). Glucuronidation catalyzed by UDPglucuronosyltransferases (UGTs) is one of the major steps responsible for the metabolism of many drugs, environmental chemicals and endogenous compounds. Pharmacokinetic behaviours of drugs could be altered by inhibition of these UGT isoforms, and the search for drugs that potentially inhibit these UGT isoforms is very significant from a clinical point of view. In the present study, inhibition of five important UGT isoforms in human liver (UGT1A1, 1A3, 1A6, 1A9 and 2B7) by CMA was investigated using 4-MU as nonspecific substrate and recombinant UGT isoforms as enzyme sources. The results showed that CMA exhibited inhibitory effects on UGT1A3 (IC50 = 8.6 ± 1.4 M) and UGT2B7 (IC50 = 14.2 ± 3.8 M), with other UGT isoforms negligibly influenced. Lineweaver-Burk and Dixon plots showed that CMA noncompetitively inhibited UGT1A3 and UGT2B7. The Ki value was calculated to be 36.9 M and 4.1 M for UGT1A3 and UGT2B7, respectively. Considering that UGT1A3 and UGT2B7 are involved in the metabolism of many drugs, special attentions should be paid when CMA was co-administered with the drugs which mainly underwent UGT1A3, 2B7-mediated metabolism.
No References for this article.
No Supplementary Data.
No Article Media
No Metrics

Document Type: Research Article

Publication date: 01 March 2011

More about this publication?
  • Pharmazie is a leading journal in the field of pharmaceutical sciences. As a peer-reviewed scientific journal, Pharmazie is regularly indexed in the relevant databases like Web of science, Journal Citation Reports and many others. The journal is open for submissions from the whole spectrum of pharnaceutical sciences including Pharmaceutical Chemistry, Experimental and Clinical Pharmacology, Drug Analysis, Pharmaceutics, Pharmaceutical Biology, Clinical Pharmacy etc.
  • Information for Authors
  • Submit a Paper
  • Subscribe to this Title
  • Ingenta Connect is not responsible for the content or availability of external websites
  • Access Key
  • Free content
  • Partial Free content
  • New content
  • Open access content
  • Partial Open access content
  • Subscribed content
  • Partial Subscribed content
  • Free trial content
Cookie Policy
Cookie Policy
Ingenta Connect website makes use of cookies so as to keep track of data that you have filled in. I am Happy with this Find out more