Effects of the CYP2C913 allele on the pharmacokinetics of losartan in healthy male subjects
The aim of the study was to determine the pharmacokinetics of losartan in relation to the CYP2C9*13 allele. A single oral dose of 50 mg losartan was administrated to each of the 16 healthy male volunteers with a different genotype (CYP2C9*1/*1, n = 6; CYP2C9*1/*13, n = 4; and CYP2C9*1/*3, n = 6). Bl...
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| creator | Li, Z. Wang, G. Wang, L.-S. Zhang, W. Tan, Z.-R. Fan, L. Chen, B.-L. Li, Q. Liu, J. Tu, J.-H. Hu, D.-L. Liu, Z.-Q. Zhou, H.-H. |
| description | The aim of the study was to determine the pharmacokinetics of losartan in relation to the CYP2C9*13 allele.
A single oral dose of 50 mg losartan was administrated to each of the 16 healthy male volunteers with a different genotype (CYP2C9*1/*1, n = 6; CYP2C9*1/*13, n = 4; and CYP2C9*1/*3, n = 6). Blood samples were collected from pre-dose up to 24 h after the drug administration. Plasma losartan and E3174 (an active metabolite of losartan) were assayed by liquid chromatography-tandem mass spectrometry (LC-MS/MS).
All the subjects finished the study without adverse drug effects. In the present study, the frequencies of CYP2C9*13 and *13 alleles were 0.6% and 2.6% in Chinese healthy volunteers, respectively, and both alleles were in Hardy-Weinberg equilibrium. Compared with the subjects in the CYP2C9*1/*1 group, individuals carrying the CYP2C9*1/*13 genotype showed significantly a longer t1/2 of losartan and E3174 and markedly increased the area under the curve (AUC) of losartan. Meanwhile, the CYP2C9*1/*3 genotype group had significant differences in t1/2 and Cmax of E3174 compared with the CYP2C9*1/*1 group. The ratio of AUCE3174/AUClosartan after losartan administration in the CYP2C9*1/*13 and CYP2C9*1/*3 groups was also statistically different from that in the CYP2C9*1/*1 group.
The data indicate that the presence of the CYP2C9*13 allele results in poor metabolism of losartan after a single oral dose. |
| doi_str_mv | 10.1080/00498250903134435 |
| format | Article |
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A single oral dose of 50 mg losartan was administrated to each of the 16 healthy male volunteers with a different genotype (CYP2C9*1/*1, n = 6; CYP2C9*1/*13, n = 4; and CYP2C9*1/*3, n = 6). Blood samples were collected from pre-dose up to 24 h after the drug administration. Plasma losartan and E3174 (an active metabolite of losartan) were assayed by liquid chromatography-tandem mass spectrometry (LC-MS/MS).
All the subjects finished the study without adverse drug effects. In the present study, the frequencies of CYP2C9*13 and *13 alleles were 0.6% and 2.6% in Chinese healthy volunteers, respectively, and both alleles were in Hardy-Weinberg equilibrium. Compared with the subjects in the CYP2C9*1/*1 group, individuals carrying the CYP2C9*1/*13 genotype showed significantly a longer t1/2 of losartan and E3174 and markedly increased the area under the curve (AUC) of losartan. Meanwhile, the CYP2C9*1/*3 genotype group had significant differences in t1/2 and Cmax of E3174 compared with the CYP2C9*1/*1 group. The ratio of AUCE3174/AUClosartan after losartan administration in the CYP2C9*1/*13 and CYP2C9*1/*3 groups was also statistically different from that in the CYP2C9*1/*1 group.
The data indicate that the presence of the CYP2C9*13 allele results in poor metabolism of losartan after a single oral dose.</description><identifier>ISSN: 0049-8254</identifier><identifier>EISSN: 1366-5928</identifier><identifier>DOI: 10.1080/00498250903134435</identifier><identifier>PMID: 19604036</identifier><language>eng</language><publisher>England: Informa UK Ltd</publisher><subject>Administration, Oral ; Alleles ; Antihypertensive Agents - administration & dosage ; Antihypertensive Agents - pharmacokinetics ; Aryl Hydrocarbon Hydroxylases - genetics ; Asian Continental Ancestry Group - genetics ; CYP2C9 ; Cytochrome P-450 CYP2C9 ; E3174 ; Gene Frequency ; Humans ; Imidazoles - pharmacokinetics ; lorartan ; Losartan - administration & dosage ; Losartan - pharmacokinetics ; Male ; pharmacokinetics ; polymorphism ; Tetrazoles - pharmacokinetics ; Young Adult</subject><ispartof>Xenobiotica, 2009-10, Vol.39 (10), p.788-793</ispartof><rights>2009 Informa UK Ltd 2009</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c405t-2efd5e6c20bfea68686ec3f7985c30e42d5e2ab6639b95acf23d79a6fdd1f30c3</citedby><cites>FETCH-LOGICAL-c405t-2efd5e6c20bfea68686ec3f7985c30e42d5e2ab6639b95acf23d79a6fdd1f30c3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.tandfonline.com/doi/pdf/10.1080/00498250903134435$$EPDF$$P50$$Ginformaworld$$H</linktopdf><linktohtml>$$Uhttps://www.tandfonline.com/doi/full/10.1080/00498250903134435$$EHTML$$P50$$Ginformaworld$$H</linktohtml><link.rule.ids>314,780,784,27924,27925,59647,59753,60436,60542,61221,61256,61402,61437</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/19604036$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Li, Z.</creatorcontrib><creatorcontrib>Wang, G.</creatorcontrib><creatorcontrib>Wang, L.-S.</creatorcontrib><creatorcontrib>Zhang, W.</creatorcontrib><creatorcontrib>Tan, Z.-R.</creatorcontrib><creatorcontrib>Fan, L.</creatorcontrib><creatorcontrib>Chen, B.-L.</creatorcontrib><creatorcontrib>Li, Q.</creatorcontrib><creatorcontrib>Liu, J.</creatorcontrib><creatorcontrib>Tu, J.-H.</creatorcontrib><creatorcontrib>Hu, D.-L.</creatorcontrib><creatorcontrib>Liu, Z.-Q.</creatorcontrib><creatorcontrib>Zhou, H.-H.</creatorcontrib><title>Effects of the CYP2C913 allele on the pharmacokinetics of losartan in healthy male subjects</title><title>Xenobiotica</title><addtitle>Xenobiotica</addtitle><description>The aim of the study was to determine the pharmacokinetics of losartan in relation to the CYP2C9*13 allele.
A single oral dose of 50 mg losartan was administrated to each of the 16 healthy male volunteers with a different genotype (CYP2C9*1/*1, n = 6; CYP2C9*1/*13, n = 4; and CYP2C9*1/*3, n = 6). Blood samples were collected from pre-dose up to 24 h after the drug administration. Plasma losartan and E3174 (an active metabolite of losartan) were assayed by liquid chromatography-tandem mass spectrometry (LC-MS/MS).
All the subjects finished the study without adverse drug effects. In the present study, the frequencies of CYP2C9*13 and *13 alleles were 0.6% and 2.6% in Chinese healthy volunteers, respectively, and both alleles were in Hardy-Weinberg equilibrium. Compared with the subjects in the CYP2C9*1/*1 group, individuals carrying the CYP2C9*1/*13 genotype showed significantly a longer t1/2 of losartan and E3174 and markedly increased the area under the curve (AUC) of losartan. Meanwhile, the CYP2C9*1/*3 genotype group had significant differences in t1/2 and Cmax of E3174 compared with the CYP2C9*1/*1 group. The ratio of AUCE3174/AUClosartan after losartan administration in the CYP2C9*1/*13 and CYP2C9*1/*3 groups was also statistically different from that in the CYP2C9*1/*1 group.
The data indicate that the presence of the CYP2C9*13 allele results in poor metabolism of losartan after a single oral dose.</description><subject>Administration, Oral</subject><subject>Alleles</subject><subject>Antihypertensive Agents - administration & dosage</subject><subject>Antihypertensive Agents - pharmacokinetics</subject><subject>Aryl Hydrocarbon Hydroxylases - genetics</subject><subject>Asian Continental Ancestry Group - genetics</subject><subject>CYP2C9</subject><subject>Cytochrome P-450 CYP2C9</subject><subject>E3174</subject><subject>Gene Frequency</subject><subject>Humans</subject><subject>Imidazoles - pharmacokinetics</subject><subject>lorartan</subject><subject>Losartan - administration & dosage</subject><subject>Losartan - pharmacokinetics</subject><subject>Male</subject><subject>pharmacokinetics</subject><subject>polymorphism</subject><subject>Tetrazoles - pharmacokinetics</subject><subject>Young Adult</subject><issn>0049-8254</issn><issn>1366-5928</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2009</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp9kMFq3DAQhkVIaTbbPkAuxbec3I4kW2uRXMKSNoVAe2gPpQcxlkest7K1lWzKvn212YVQCkEHgeb7f0YfY1cc3nNo4ANApRtRgwbJZVXJ-owtuFSqrLVoztniMC8zUF2wy5S2AKC4EK_ZBdcKKpBqwX7eO0d2SkVwxbShYv3jq1hrLgv0njwVYXx63m0wDmjDr36kqbdPuA8J44Rj0Y_FhtBPm30xYM6kud0eOt-wVw59orene8m-f7z_tn4oH798-ry-eyxtBfVUCnJdTcoKaB2havIhK91KN7WVQJXIU4GtUlK3ukbrhOxWGpXrOu4kWLlk18feXQy_Z0qTGfpkyXscKczJrGT-6-ogaMn4kbQxpBTJmV3sB4x7w8EclJr_lObMu1P73A7UPSdODjNwewT60YVs6U-IvjMT7n2ILuJo-2TkS_03_8SPKi1GMtswxzGbe2G7v60GljY</recordid><startdate>20091001</startdate><enddate>20091001</enddate><creator>Li, Z.</creator><creator>Wang, G.</creator><creator>Wang, L.-S.</creator><creator>Zhang, W.</creator><creator>Tan, Z.-R.</creator><creator>Fan, L.</creator><creator>Chen, B.-L.</creator><creator>Li, Q.</creator><creator>Liu, J.</creator><creator>Tu, J.-H.</creator><creator>Hu, D.-L.</creator><creator>Liu, Z.-Q.</creator><creator>Zhou, H.-H.</creator><general>Informa UK Ltd</general><general>Taylor & Francis</general><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>20091001</creationdate><title>Effects of the CYP2C913 allele on the pharmacokinetics of losartan in healthy male subjects</title><author>Li, Z. ; Wang, G. ; Wang, L.-S. ; Zhang, W. ; Tan, Z.-R. ; Fan, L. ; Chen, B.-L. ; Li, Q. ; Liu, J. ; Tu, J.-H. ; Hu, D.-L. ; Liu, Z.-Q. ; Zhou, H.-H.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c405t-2efd5e6c20bfea68686ec3f7985c30e42d5e2ab6639b95acf23d79a6fdd1f30c3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2009</creationdate><topic>Administration, Oral</topic><topic>Alleles</topic><topic>Antihypertensive Agents - administration & dosage</topic><topic>Antihypertensive Agents - pharmacokinetics</topic><topic>Aryl Hydrocarbon Hydroxylases - genetics</topic><topic>Asian Continental Ancestry Group - genetics</topic><topic>CYP2C9</topic><topic>Cytochrome P-450 CYP2C9</topic><topic>E3174</topic><topic>Gene Frequency</topic><topic>Humans</topic><topic>Imidazoles - pharmacokinetics</topic><topic>lorartan</topic><topic>Losartan - administration & dosage</topic><topic>Losartan - pharmacokinetics</topic><topic>Male</topic><topic>pharmacokinetics</topic><topic>polymorphism</topic><topic>Tetrazoles - pharmacokinetics</topic><topic>Young Adult</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Li, Z.</creatorcontrib><creatorcontrib>Wang, G.</creatorcontrib><creatorcontrib>Wang, L.-S.</creatorcontrib><creatorcontrib>Zhang, W.</creatorcontrib><creatorcontrib>Tan, Z.-R.</creatorcontrib><creatorcontrib>Fan, L.</creatorcontrib><creatorcontrib>Chen, B.-L.</creatorcontrib><creatorcontrib>Li, Q.</creatorcontrib><creatorcontrib>Liu, J.</creatorcontrib><creatorcontrib>Tu, J.-H.</creatorcontrib><creatorcontrib>Hu, D.-L.</creatorcontrib><creatorcontrib>Liu, Z.-Q.</creatorcontrib><creatorcontrib>Zhou, H.-H.</creatorcontrib><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>Xenobiotica</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Li, Z.</au><au>Wang, G.</au><au>Wang, L.-S.</au><au>Zhang, W.</au><au>Tan, Z.-R.</au><au>Fan, L.</au><au>Chen, B.-L.</au><au>Li, Q.</au><au>Liu, J.</au><au>Tu, J.-H.</au><au>Hu, D.-L.</au><au>Liu, Z.-Q.</au><au>Zhou, H.-H.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Effects of the CYP2C913 allele on the pharmacokinetics of losartan in healthy male subjects</atitle><jtitle>Xenobiotica</jtitle><addtitle>Xenobiotica</addtitle><date>2009-10-01</date><risdate>2009</risdate><volume>39</volume><issue>10</issue><spage>788</spage><epage>793</epage><pages>788-793</pages><issn>0049-8254</issn><eissn>1366-5928</eissn><abstract>The aim of the study was to determine the pharmacokinetics of losartan in relation to the CYP2C9*13 allele.
A single oral dose of 50 mg losartan was administrated to each of the 16 healthy male volunteers with a different genotype (CYP2C9*1/*1, n = 6; CYP2C9*1/*13, n = 4; and CYP2C9*1/*3, n = 6). Blood samples were collected from pre-dose up to 24 h after the drug administration. Plasma losartan and E3174 (an active metabolite of losartan) were assayed by liquid chromatography-tandem mass spectrometry (LC-MS/MS).
All the subjects finished the study without adverse drug effects. In the present study, the frequencies of CYP2C9*13 and *13 alleles were 0.6% and 2.6% in Chinese healthy volunteers, respectively, and both alleles were in Hardy-Weinberg equilibrium. Compared with the subjects in the CYP2C9*1/*1 group, individuals carrying the CYP2C9*1/*13 genotype showed significantly a longer t1/2 of losartan and E3174 and markedly increased the area under the curve (AUC) of losartan. Meanwhile, the CYP2C9*1/*3 genotype group had significant differences in t1/2 and Cmax of E3174 compared with the CYP2C9*1/*1 group. The ratio of AUCE3174/AUClosartan after losartan administration in the CYP2C9*1/*13 and CYP2C9*1/*3 groups was also statistically different from that in the CYP2C9*1/*1 group.
The data indicate that the presence of the CYP2C9*13 allele results in poor metabolism of losartan after a single oral dose.</abstract><cop>England</cop><pub>Informa UK Ltd</pub><pmid>19604036</pmid><doi>10.1080/00498250903134435</doi><tpages>6</tpages></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 0049-8254 |
| ispartof | Xenobiotica, 2009-10, Vol.39 (10), p.788-793 |
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| language | eng |
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| source | MEDLINE; Taylor & Francis:Master (3349 titles); Taylor & Francis Medical Library - CRKN |
| subjects | Administration, Oral Alleles Antihypertensive Agents - administration & dosage Antihypertensive Agents - pharmacokinetics Aryl Hydrocarbon Hydroxylases - genetics Asian Continental Ancestry Group - genetics CYP2C9 Cytochrome P-450 CYP2C9 E3174 Gene Frequency Humans Imidazoles - pharmacokinetics lorartan Losartan - administration & dosage Losartan - pharmacokinetics Male pharmacokinetics polymorphism Tetrazoles - pharmacokinetics Young Adult |
| title | Effects of the CYP2C913 allele on the pharmacokinetics of losartan in healthy male subjects |
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