Metabolic profiling and cytochrome P450 reaction phenotyping of medroxyprogesterone acetate

Drug Metabolism and Disposition : the Biological Fate of Chemicals
Jiang-Wei ZhangLing Yang

Abstract

Medroxyprogesterone acetate (MPA) is one of the most frequently prescribed progestins for conception, hormone replacement therapy, and adjuvant endocrine therapy. MPA has a low oral bioavailability because of extensive metabolism; however, its metabolism was poorly documented. This study was intended to profile the phase I metabolites of MPA and the cytochrome P450 (P450) isoforms involved. After MPA was incubated with human liver microsomes and the NADPH-generating system, five main metabolites (namely M-1, M-2, M-3, M-4, and M-5) were isolated by high-performance liquid chromatography. Three major metabolites (M-2, M-4, and M-3) were tentatively identified to be 6beta-, 2beta-, and 1beta-hydroxy MPA by liquid chromatography/mass spectrometry and (1)H nuclear magnetic resonance. By consecutive metabolism of purified M-2, M-3, and M-4, M-1 and M-5 were proposed to be 2beta-, 6beta-dihydroxy MPA, and 1,2-dehydro MPA, respectively. CYP3A4 was identified to be the isoform primarily involved in the formation of M-2, M-3, and M-4 in studies with specific P450 inhibitors, recombinant P450s, and correlation analysis. Rat and minipig liver microsomes were included evaluating species differences, and the results showed little difference...Continue Reading

References

Jul 1, 1992·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·M C EtienneM Namer
Jun 1, 1990·British Journal of Clinical Pharmacology·D SesardicD S Davies
Nov 21, 2000·Obstetrics and Gynecology·S Ratchanon, S Taneepanichskul
Dec 22, 2000·Contraception·P Chotnopparatpattara, S Taneepanichskul
Apr 16, 2002·Drug Metabolism and Disposition : the Biological Fate of Chemicals·James M RaeZeruesenay Desta
Jul 19, 2002·JAMA : the Journal of the American Medical Association·Jacques E RossouwUNKNOWN Writing Group for the Women's Health Initiative Investigators
Jun 20, 2003·Drug Metabolism and Disposition : the Biological Fate of Chemicals·Kaoru KobayashiKan Chiba
Jun 26, 2003·JAMA : the Journal of the American Medical Association·Rowan T ChlebowskiUNKNOWN WHI Investigators
Jul 10, 2003·Drugs in R&D·UNKNOWN Adis International Ltd
Oct 1, 1962·The Journal of Clinical Endocrinology and Metabolism·M L HELMREICH, R A HUSEBY
Jan 8, 2004·JAMA : the Journal of the American Medical Association·Adam L HershRandall S Stafford
Mar 31, 2004·Journal of Pediatric and Adolescent Gynecology·Andrea E BonnyGail B Slap
Sep 18, 2004·European Journal of Biochemistry·Joel A KrauserF Peter Guengerich
Dec 8, 2004·The Journal of Adolescent Health : Official Publication of the Society for Adolescent Medicine·Barbara A CromerSara M Debanne
Dec 21, 2004·Drug Metabolism and Disposition : the Biological Fate of Chemicals·Robert L WalskyWilliam R Proctor
Apr 18, 2006·Journal of Pharmaceutical and Biomedical Analysis·Fujiang GuoYuanchao Li
Apr 29, 2006·European Journal of Clinical Pharmacology·Jiang-Wei ZhangLing Yang
Feb 12, 2008·Journal of Pharmacy & Pharmaceutical Sciences : a Publication of the Canadian Society for Pharmaceutical Sciences, Société Canadienne Des Sciences Pharmaceutiques·Jiang-Wei ZhangLing Yang

❮ Previous
Next ❯

Citations

Aug 5, 2009·Chemical & Pharmaceutical Bulletin·Jianjun ChenWei Li
Dec 3, 2013·The Journal of Steroid Biochemistry and Molecular Biology·Frank Z Stanczyk, Bhagu R Bhavnani
Jul 3, 2015·International Journal of Molecular Sciences·Zi-Ru DaiLing Yang
May 29, 2009·Expert Opinion on Drug Metabolism & Toxicology·Yan-Yan Zhang, Ling Yang
Aug 21, 2015·The Journal of Steroid Biochemistry and Molecular Biology·Frank Z Stanczyk, Bhagu R Bhavnani
Jun 12, 2014·Xenobiotica; the Fate of Foreign Compounds in Biological Systems·Dongxue SunLing Yang
Dec 1, 2010·European Journal of Pharmacology·Vijayakumar SukumaranYoshifusa Aizawa
Jul 3, 2009·Xenobiotica; the Fate of Foreign Compounds in Biological Systems·H-X LiuL Yang
Dec 17, 2009·Xenobiotica; the Fate of Foreign Compounds in Biological Systems·Y-F CaoL Yang
Feb 24, 2010·Drug Metabolism and Disposition : the Biological Fate of Chemicals·Si-Cheng LiangLing Yang
Apr 24, 2009·Xenobiotica; the Fate of Foreign Compounds in Biological Systems·H-X LiuL Yang
Oct 3, 2009·Xenobiotica; the Fate of Foreign Compounds in Biological Systems·Y-Y ZhangL Yang
Dec 15, 2020·Pharmacology & Therapeutics·Alexis J BickJanet P Hapgood

❮ Previous
Next ❯

Related Concepts

Trending Feeds

COVID-19

Coronaviruses encompass a large family of viruses that cause the common cold as well as more serious diseases, such as the ongoing outbreak of coronavirus disease 2019 (COVID-19; formally known as 2019-nCoV). Coronaviruses can spread from animals to humans; symptoms include fever, cough, shortness of breath, and breathing difficulties; in more severe cases, infection can lead to death. This feed covers recent research on COVID-19.

Blastomycosis

Blastomycosis fungal infections spread through inhaling Blastomyces dermatitidis spores. Discover the latest research on blastomycosis fungal infections here.

Nuclear Pore Complex in ALS/FTD

Alterations in nucleocytoplasmic transport, controlled by the nuclear pore complex, may be involved in the pathomechanism underlying multiple neurodegenerative diseases including Amyotrophic Lateral Sclerosis and Frontotemporal Dementia. Here is the latest research on the nuclear pore complex in ALS and FTD.

Applications of Molecular Barcoding

The concept of molecular barcoding is that each original DNA or RNA molecule is attached to a unique sequence barcode. Sequence reads having different barcodes represent different original molecules, while sequence reads having the same barcode are results of PCR duplication from one original molecule. Discover the latest research on molecular barcoding here.

Chronic Fatigue Syndrome

Chronic fatigue syndrome is a disease characterized by unexplained disabling fatigue; the pathology of which is incompletely understood. Discover the latest research on chronic fatigue syndrome here.

Evolution of Pluripotency

Pluripotency refers to the ability of a cell to develop into three primary germ cell layers of the embryo. This feed focuses on the mechanisms that underlie the evolution of pluripotency. Here is the latest research.

Position Effect Variegation

Position Effect Variagation occurs when a gene is inactivated due to its positioning near heterochromatic regions within a chromosome. Discover the latest research on Position Effect Variagation here.

STING Receptor Agonists

Stimulator of IFN genes (STING) are a group of transmembrane proteins that are involved in the induction of type I interferon that is important in the innate immune response. The stimulation of STING has been an active area of research in the treatment of cancer and infectious diseases. Here is the latest research on STING receptor agonists.

Microbicide

Microbicides are products that can be applied to vaginal or rectal mucosal surfaces with the goal of preventing, or at least significantly reducing, the transmission of sexually transmitted infections. Here is the latest research on microbicides.