Influence of CYP3A5 genetic polymorphism on cyclosporine A metabolism and elimination in Chinese renal transplant recipients

Aim: To investigate whether the CYP3A5*3 polymorphism would affect cyclosporine A (CsA) metabolism in Chinese renal transplant patients. Methods: The CYP3A5*3 genotype was determined in Chinese renal transplant recipients using polymerase chain reaction and amplification of specific alleles (PCR-ASA...

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Veröffentlicht in:Acta pharmacologica Sinica 2006-11, Vol.27 (11), p.1504-1508
Hauptverfasser: CHU, Xiao‐man, HAO, Hai‐ping, WANG, Guang‐ji, GUO, Lian‐qing, MIN, Pei‐qing
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container_title Acta pharmacologica Sinica
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creator CHU, Xiao‐man
HAO, Hai‐ping
WANG, Guang‐ji
GUO, Lian‐qing
MIN, Pei‐qing
description Aim: To investigate whether the CYP3A5*3 polymorphism would affect cyclosporine A (CsA) metabolism in Chinese renal transplant patients. Methods: The CYP3A5*3 genotype was determined in Chinese renal transplant recipients using polymerase chain reaction and amplification of specific alleles (PCR-ASA). The concentrations of CsA and metabolites were separately measured by fluorescence polarization immunoassay and dose-adjusted trough concentrations and metabolic ratio (MR) values were calculated. Results: The trough concentrations adjusted with the dose was significantly higher in the wild allele carriers compared to both the homozygous (*3*3) and heterozygous variants (*1*3). However, no significant difference was found for the dose-adjusted metabolite concentrations. The MR values for the 3 genotype groups were as follows: 0.92±0.62 for CYP3A5*3/ *3 (n=14), 0.99±0.51 for CYP3A5*1/*3 (n=15), and 1.45±0.62 for CYP3A5*1/*1 (n=9), respectively. Post hoc comparisons showed that only the MR values between the CYP3A5*3/*3 group and the CYP3A5*1/*1 group were significantly different. Conclusion: The CYP3A5*3 polymorphism exerted little effect on cyclosporine metabolism. The MR may be a more accurate indicator for therapeutic drug monitoring, considering its integrated information on body exposure of both parent drugs and metabolites.
doi_str_mv 10.1111/j.1745-7254.2006.00428.x
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Methods: The CYP3A5*3 genotype was determined in Chinese renal transplant recipients using polymerase chain reaction and amplification of specific alleles (PCR-ASA). The concentrations of CsA and metabolites were separately measured by fluorescence polarization immunoassay and dose-adjusted trough concentrations and metabolic ratio (MR) values were calculated. Results: The trough concentrations adjusted with the dose was significantly higher in the wild allele carriers compared to both the homozygous (*3*3) and heterozygous variants (*1*3). However, no significant difference was found for the dose-adjusted metabolite concentrations. The MR values for the 3 genotype groups were as follows: 0.92±0.62 for CYP3A5*3/ *3 (n=14), 0.99±0.51 for CYP3A5*1/*3 (n=15), and 1.45±0.62 for CYP3A5*1/*1 (n=9), respectively. Post hoc comparisons showed that only the MR values between the CYP3A5*3/*3 group and the CYP3A5*1/*1 group were significantly different. Conclusion: The CYP3A5*3 polymorphism exerted little effect on cyclosporine metabolism. The MR may be a more accurate indicator for therapeutic drug monitoring, considering its integrated information on body exposure of both parent drugs and metabolites.</description><identifier>ISSN: 1671-4083</identifier><identifier>EISSN: 1745-7254</identifier><identifier>DOI: 10.1111/j.1745-7254.2006.00428.x</identifier><identifier>PMID: 17049128</identifier><language>eng</language><publisher>Melbourne, Australia: Blackwell Publishing Asia</publisher><subject>Adult ; Asian Continental Ancestry Group ; China ; cyclosporine ; Cyclosporine - metabolism ; CYP3A5 ; Cytochrome P-450 CYP3A ; Cytochrome P-450 Enzyme System - genetics ; DNA Primers ; Female ; genetic polymorphism ; Genotype ; Humans ; Kidney Transplantation ; Male ; metabolic ratio ; Middle Aged ; Polymorphism, Genetic ; renal transplant patients ; 新陈代谢 ; 环孢霉素 ; 遗传多态性</subject><ispartof>Acta pharmacologica Sinica, 2006-11, Vol.27 (11), p.1504-1508</ispartof><rights>Copyright Nature Publishing Group Nov 2006</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c5028-9be33e15dd077b5c8672019d7f3771b30acb6c6869ce7cc11b217d6a7c8b79503</citedby><cites>FETCH-LOGICAL-c5028-9be33e15dd077b5c8672019d7f3771b30acb6c6869ce7cc11b217d6a7c8b79503</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Uhttp://image.cqvip.com/vip1000/qk/95561A/95561A.jpg</thumbnail><linktopdf>$$Uhttps://onlinelibrary.wiley.com/doi/pdf/10.1111%2Fj.1745-7254.2006.00428.x$$EPDF$$P50$$Gwiley$$H</linktopdf><linktohtml>$$Uhttps://onlinelibrary.wiley.com/doi/full/10.1111%2Fj.1745-7254.2006.00428.x$$EHTML$$P50$$Gwiley$$H</linktohtml><link.rule.ids>314,776,780,1411,27901,27902,45550,45551</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/17049128$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>CHU, Xiao‐man</creatorcontrib><creatorcontrib>HAO, Hai‐ping</creatorcontrib><creatorcontrib>WANG, Guang‐ji</creatorcontrib><creatorcontrib>GUO, Lian‐qing</creatorcontrib><creatorcontrib>MIN, Pei‐qing</creatorcontrib><title>Influence of CYP3A5 genetic polymorphism on cyclosporine A metabolism and elimination in Chinese renal transplant recipients</title><title>Acta pharmacologica Sinica</title><addtitle>Acta Pharmacologica Sinica</addtitle><description>Aim: To investigate whether the CYP3A5*3 polymorphism would affect cyclosporine A (CsA) metabolism in Chinese renal transplant patients. Methods: The CYP3A5*3 genotype was determined in Chinese renal transplant recipients using polymerase chain reaction and amplification of specific alleles (PCR-ASA). The concentrations of CsA and metabolites were separately measured by fluorescence polarization immunoassay and dose-adjusted trough concentrations and metabolic ratio (MR) values were calculated. Results: The trough concentrations adjusted with the dose was significantly higher in the wild allele carriers compared to both the homozygous (*3*3) and heterozygous variants (*1*3). However, no significant difference was found for the dose-adjusted metabolite concentrations. The MR values for the 3 genotype groups were as follows: 0.92±0.62 for CYP3A5*3/ *3 (n=14), 0.99±0.51 for CYP3A5*1/*3 (n=15), and 1.45±0.62 for CYP3A5*1/*1 (n=9), respectively. Post hoc comparisons showed that only the MR values between the CYP3A5*3/*3 group and the CYP3A5*1/*1 group were significantly different. Conclusion: The CYP3A5*3 polymorphism exerted little effect on cyclosporine metabolism. 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Methods: The CYP3A5*3 genotype was determined in Chinese renal transplant recipients using polymerase chain reaction and amplification of specific alleles (PCR-ASA). The concentrations of CsA and metabolites were separately measured by fluorescence polarization immunoassay and dose-adjusted trough concentrations and metabolic ratio (MR) values were calculated. Results: The trough concentrations adjusted with the dose was significantly higher in the wild allele carriers compared to both the homozygous (*3*3) and heterozygous variants (*1*3). However, no significant difference was found for the dose-adjusted metabolite concentrations. The MR values for the 3 genotype groups were as follows: 0.92±0.62 for CYP3A5*3/ *3 (n=14), 0.99±0.51 for CYP3A5*1/*3 (n=15), and 1.45±0.62 for CYP3A5*1/*1 (n=9), respectively. Post hoc comparisons showed that only the MR values between the CYP3A5*3/*3 group and the CYP3A5*1/*1 group were significantly different. Conclusion: The CYP3A5*3 polymorphism exerted little effect on cyclosporine metabolism. The MR may be a more accurate indicator for therapeutic drug monitoring, considering its integrated information on body exposure of both parent drugs and metabolites.</abstract><cop>Melbourne, Australia</cop><pub>Blackwell Publishing Asia</pub><pmid>17049128</pmid><doi>10.1111/j.1745-7254.2006.00428.x</doi><tpages>5</tpages><oa>free_for_read</oa></addata></record>
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subjects Adult
Asian Continental Ancestry Group
China
cyclosporine
Cyclosporine - metabolism
CYP3A5
Cytochrome P-450 CYP3A
Cytochrome P-450 Enzyme System - genetics
DNA Primers
Female
genetic polymorphism
Genotype
Humans
Kidney Transplantation
Male
metabolic ratio
Middle Aged
Polymorphism, Genetic
renal transplant patients
新陈代谢
环孢霉素
遗传多态性
title Influence of CYP3A5 genetic polymorphism on cyclosporine A metabolism and elimination in Chinese renal transplant recipients
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