PMID: 11908770Mar 23, 2002Paper

CYP2C9*3 influences the metabolism and the drug-interaction of candesartan in vitro

The Pharmacogenomics Journal
Tadaaki HanataniJunichi Azuma

Abstract

Candesartan cilexetil is an angiotensin II receptor antagonist, and candesartan, its active metabolite, is metabolized by CYP2C9. However, the effect of CYP2C9*3 on candesartan metabolism is not established. We characterized the kinetics of candesartan by CYP2C9*1/*1 and CYP2C9*1/*3 in human liver microsomes. The difference between the two was not significant. Subsequently, CYP2C9*1 and CYP2C9*3 (Leu359) were expressed in yeast, and the kinetics of candesartan were determined. The wild-type showed the lower Km (345 vs 439 microM; 3/4) and higher Vmax/Km (1/3) than the Leu359 variant. Also, we investigated potential interaction between candesartan and warfarin with both the wild-type and the Leu359 variant. Candesartan had no effect on S-warfarin 7-hydroxylation. In contrast, S-warfarin inhibited candesartan metabolism by the wild-type (K = 17microM) greater than by the Leu359 variant (Ki = 36 microM). These findings suggest that CYP2C9*3 may change not only the metabolic activity but also the inhibitory susceptibility compared with CYP2C9*1.

References

Aug 1, 1996·Pharmacogenetics·T H Sullivan-KloseJ A Goldstein
Feb 23, 1996·Journal of Chromatography. B, Biomedical Applications·T MiyabayashiT Yashiki
Nov 14, 1997·Pharmacogenetics·D J StewardA E Rettie
Nov 14, 1997·Pharmacogenetics·K NasuT Ishizaki
Jan 22, 1998·Archives of Biochemistry and Biophysics·J WanY Funae
Jul 15, 1998·British Journal of Clinical Pharmacology·J O Miners, D J Birkett
May 10, 2000·Pharmacogenetics·J O MinersJ A Goldstein
Jul 6, 2000·European Journal of Clinical Pharmacology·P TaavitsainenO Pelkonen

❮ Previous
Next ❯

Citations

Nov 2, 2011·Drug Metabolism and Pharmacokinetics·Masahiro Hiratsuka
Jun 12, 2013·The Pharmacogenomics Journal·Y NiinumaM Hiratsuka
Dec 20, 2007·American Journal of Hypertension·Vincent J CanzanelloArlene B Chapman
Mar 21, 2007·Chemistry & Biodiversity·Bernard Testa, Stefanie D Krämer
Nov 3, 2012·Drug Metabolism and Disposition : the Biological Fate of Chemicals·Teresa CabaleiroFrancisco Abad-Santos
Sep 14, 2006·Pharmacological Reviews·Sharon J Gardiner, Evan J Begg
Dec 1, 2004·Personalized Medicine·Julia KirchheinerJürgen Brockmöller
Apr 10, 2020·Clinical and Translational Science·Saaket AgrawalAlfred L George
Dec 14, 2004·Cardiovascular Drug Reviews·Christoph H GleiterKlaus Mörike
Sep 1, 2006·Nihon yakurigaku zasshi. Folia pharmacologica Japonica·Toshiro NiwaAkira Takagi
May 30, 2003·Journal of Medicinal Chemistry·Boris Schmidt, Bernhard Schieffer

❮ Previous
Next ❯

Related Concepts

Related Feeds

Anthelmintics

Anthelmintics or antihelminthics are a group of antiparasitic drugs that expel parasitic worms (helminths) and other internal parasites from the body by either stunning or killing them and without causing significant damage to the host. Discover the latest research on anthelmintics here.

Antihypertensive Agents: Mechanisms of Action

Antihypertensive drugs are used to treat hypertension (high blood pressure) which aims to prevent the complications of high blood pressure, such as stroke and myocardial infarction. Discover the latest research on antihypertensive drugs and their mechanism of action here.