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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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| Published in: | Clinical pharmacology and therapeutics 2003-11, Vol.74 (5), p.505-508 |
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| container_issue | 5 |
| container_start_page | 505 |
| container_title | Clinical pharmacology and therapeutics |
| container_volume | 74 |
| creator | Uchida, Shinya Watanabe, Hiroshi Nishio, Shinichiro Hashimoto, Hisakuni Yamazaki, Keisuke Hayashi, Hideharu Ohashi, Kyoichi |
| description | 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 |
| doi_str_mv | 10.1016/j.clpt.2003.08.001 |
| format | article |
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Clinical Pharmacology & Therapeutics (2003) 74, 505–508; doi: 10.1016/j.clpt.2003.08.001</description><subject>Aged</subject><subject>Aged, 80 and over</subject><subject>Angiotensin II Type 1 Receptor Blockers</subject><subject>Antihypertensive agents</subject><subject>Antihypertensive Agents - pharmacokinetics</subject><subject>Antihypertensive Agents - pharmacology</subject><subject>Area Under Curve</subject><subject>Aryl Hydrocarbon Hydroxylases - genetics</subject><subject>Benzimidazoles - pharmacokinetics</subject><subject>Benzimidazoles - pharmacology</subject><subject>Biological and medical sciences</subject><subject>Blood Pressure - drug effects</subject><subject>Blood Pressure - genetics</subject><subject>Cardiovascular system</subject><subject>Cytochrome P-450 CYP2C9</subject><subject>Genotype</subject><subject>Heart Failure - drug therapy</subject><subject>Heart Failure - genetics</subject><subject>Heart Failure - physiopathology</subject><subject>Humans</subject><subject>Hypertension - drug therapy</subject><subject>Hypertension - genetics</subject><subject>Hypertension - physiopathology</subject><subject>Male</subject><subject>Medical sciences</subject><subject>Pharmacology. Drug treatments</subject><subject>Polymorphism, Genetic</subject><subject>Tetrazoles - pharmacokinetics</subject><subject>Tetrazoles - pharmacology</subject><issn>0009-9236</issn><issn>1532-6535</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2003</creationdate><recordtype>article</recordtype><recordid>eNqNkEtv00AQgFeIiobCH-CA9kJvdvdpry9IlVUKUqTmEA6cVuP1mGxw1q5305J_X4dE6pXTPPTNjOYj5BNnOWe8uNnmrh9TLhiTOTM5Y_wNWXAtRVZoqd-SBWOsyiohi0vyPsbtXKrKmHfkkittClnxBXm87RNO2NJxA9MO3PDHB0zeRQqhpfjXYYz-CenmMA4Jw78cuw5dokNH3QxhhClBoD5QoCMkjyHRZ582NG2Q1r9Woq74jaS_MQzpMOIHctFBH_HjOV6Rn9_u1vX3bPlw_6O-XWZOGiWzBhvZAGeArWoqA6UxDkrdOcaEVqJQEoExrRrQrlVlo5So0GguS92CKZi8ItenveM0PO4xJrvz0WHfQ8BhH23JpZjVqRkUJ9BNQ4wTdnac_A6mg-XMHkXbrT2KtkfRlhk7i56HPp-375sdtq8jZ7Mz8OUMQHTQdxME5-Mrp4UuhBAz9_XEPfseD_9x2tardb1crY-t-V35AuXAmvM</recordid><startdate>200311</startdate><enddate>200311</enddate><creator>Uchida, Shinya</creator><creator>Watanabe, Hiroshi</creator><creator>Nishio, Shinichiro</creator><creator>Hashimoto, Hisakuni</creator><creator>Yamazaki, Keisuke</creator><creator>Hayashi, Hideharu</creator><creator>Ohashi, Kyoichi</creator><general>Nature Publishing</general><scope>IQODW</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7X8</scope></search><sort><creationdate>200311</creationdate><title>Altered pharmacokinetics and excessive hypotensive effect of candesartan in a patient with the CYP2C91/3 genotype</title><author>Uchida, Shinya ; Watanabe, Hiroshi ; Nishio, Shinichiro ; Hashimoto, Hisakuni ; Yamazaki, Keisuke ; Hayashi, Hideharu ; Ohashi, Kyoichi</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c3843-beb3ba10aed4b98a788ca75fc002542643ea0054ba5cd47b4429e851375da8603</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2003</creationdate><topic>Aged</topic><topic>Aged, 80 and over</topic><topic>Angiotensin II Type 1 Receptor Blockers</topic><topic>Antihypertensive agents</topic><topic>Antihypertensive Agents - pharmacokinetics</topic><topic>Antihypertensive Agents - pharmacology</topic><topic>Area Under Curve</topic><topic>Aryl Hydrocarbon Hydroxylases - genetics</topic><topic>Benzimidazoles - pharmacokinetics</topic><topic>Benzimidazoles - pharmacology</topic><topic>Biological and medical sciences</topic><topic>Blood Pressure - drug effects</topic><topic>Blood Pressure - genetics</topic><topic>Cardiovascular system</topic><topic>Cytochrome P-450 CYP2C9</topic><topic>Genotype</topic><topic>Heart Failure - drug therapy</topic><topic>Heart Failure - genetics</topic><topic>Heart Failure - physiopathology</topic><topic>Humans</topic><topic>Hypertension - drug therapy</topic><topic>Hypertension - genetics</topic><topic>Hypertension - physiopathology</topic><topic>Male</topic><topic>Medical sciences</topic><topic>Pharmacology. Drug treatments</topic><topic>Polymorphism, Genetic</topic><topic>Tetrazoles - pharmacokinetics</topic><topic>Tetrazoles - pharmacology</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Uchida, Shinya</creatorcontrib><creatorcontrib>Watanabe, Hiroshi</creatorcontrib><creatorcontrib>Nishio, Shinichiro</creatorcontrib><creatorcontrib>Hashimoto, Hisakuni</creatorcontrib><creatorcontrib>Yamazaki, Keisuke</creatorcontrib><creatorcontrib>Hayashi, Hideharu</creatorcontrib><creatorcontrib>Ohashi, Kyoichi</creatorcontrib><collection>Pascal-Francis</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><jtitle>Clinical pharmacology and therapeutics</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Uchida, Shinya</au><au>Watanabe, Hiroshi</au><au>Nishio, Shinichiro</au><au>Hashimoto, Hisakuni</au><au>Yamazaki, Keisuke</au><au>Hayashi, Hideharu</au><au>Ohashi, Kyoichi</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Altered pharmacokinetics and excessive hypotensive effect of candesartan in a patient with the CYP2C91/3 genotype</atitle><jtitle>Clinical pharmacology and therapeutics</jtitle><addtitle>Clin Pharmacol Ther</addtitle><date>2003-11</date><risdate>2003</risdate><volume>74</volume><issue>5</issue><spage>505</spage><epage>508</epage><pages>505-508</pages><issn>0009-9236</issn><eissn>1532-6535</eissn><coden>CLPTAT</coden><abstract>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.
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| 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 |
| title | Altered pharmacokinetics and excessive hypotensive effect of candesartan in a patient with the CYP2C91/3 genotype |
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