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Altered pharmacokinetics and excessive hypotensive effect of candesartan in a patient with the CYP2C9*1/*3 genotype
Author(s) -
Uchida Shinya,
Watanabe Hiroshi,
Nishio Shinichiro,
Hashimoto Hisakuni,
Yamazaki Keisuke,
Hayashi Hideharu,
Ohashi Kyoichi
Publication year - 2003
Publication title -
clinical pharmacology and therapeutics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.941
H-Index - 188
eISSN - 1532-6535
pISSN - 0009-9236
DOI - 10.1016/j.clpt.2003.08.001
Subject(s) - candesartan , medicine , clinical pharmacology , doxazosin , valsartan , pharmacology , pharmacokinetics , cyp2c9 , atenolol , chlorthalidone , endocrinology , blood pressure , angiotensin ii , cytochrome p450 , metabolism
An 89‐year‐old man with severe hypertension (190/82 mm Hg) and chronic heart failure (New York Heart Association class II) despite treatment with benidipine, doxazosin mesylate (INN, doxazosin), and furosemide was given oral candesartan cilexetil (4 mg/d), an angiotensin II type 1 receptor blocker metabolized via cytochrome P450 (CYP) 2C9. Two days later, he started to have severe dizziness and returned to the hospital on the fourth day without taking any of his medications. The blood pressure 30 hours after the last dose of candesartan was 126/64 mm Hg. Polymorphism analysis revealed the heterozygous poor metabolizer genotype CYP2C9*1/*3 . The area under the concentration‐time curve and the mean residence time of candesartan were both increased 2.5‐fold, and the oral clearance of candesartan was 48% lower than that of the average elderly Japanese patient with hypertension. These results suggest that the CYP2C9*1/*3 genotype could be associated with decreased clearance and increased plasma concentration of candesartan, potentially enhancing its hypotensive effect. Clinical Pharmacology & Therapeutics (2003) 74 , 505–508; doi: 10.1016/j.clpt.2003.08.001