Altered pharmacokinetics and excessive hypotensive effect of candesartan in a patient with the CYP2C91/3 genotype

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 m...

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Bibliographic Details
Published in:Clinical pharmacology and therapeutics 2003-11, Vol.74 (5), p.505-508
Main Authors: Uchida, Shinya, Watanabe, Hiroshi, Nishio, Shinichiro, Hashimoto, Hisakuni, Yamazaki, Keisuke, Hayashi, Hideharu, Ohashi, Kyoichi
Format: Article
Language:English
Subjects:
Aged
Aged, 80 and over
Angiotensin II Type 1 Receptor Blockers
Antihypertensive agents
Antihypertensive Agents - pharmacokinetics
Antihypertensive Agents - pharmacology
Area Under Curve
Aryl Hydrocarbon Hydroxylases - genetics
Benzimidazoles - pharmacokinetics
Benzimidazoles - pharmacology
Biological and medical sciences
Blood Pressure - drug effects
Blood Pressure - genetics
Cardiovascular system
Cytochrome P-450 CYP2C9
Genotype
Heart Failure - drug therapy
Heart Failure - genetics
Heart Failure - physiopathology
Humans
Hypertension - drug therapy
Hypertension - genetics
Hypertension - physiopathology
Male
Medical sciences
Pharmacology. Drug treatments
Polymorphism, Genetic
Tetrazoles - pharmacokinetics
Tetrazoles - pharmacology
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Summary: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
ISSN:0009-9236
1532-6535
DOI:10.1016/j.clpt.2003.08.001