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10.1208/s12248-013-9535-x http://scihub22266oqcxt.onion/10.1208/s12248-013-9535-x 24357089GeneticPolymorphismsofMetabolicEnzymesandthePharmacokineticsofIndapamideinTaiwaneseSubjects.!3933584!24357089     free     free     free Deprecated: Implicit conversion from float 229.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 229.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 229.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 229.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 229.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 229.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534       AAPS+J 2014 ; 16 (2): 206-13 Nephropedia Template TP {{tp|p=24357089|t=2014. Genetic polymorphisms of metabolic enzymes and the pharmacokinetics of indapamide in Taiwanese subjects |pdf=|usr=}}{{24357089}} gab.com Text Genetic polymorphisms of metabolic enzymes and the pharmacokinetics of indapamide in Taiwanese subjects JO: AAPS J http://www.kidney.de/pget.php?&tw=1&pmid=24357089 #FOAvip To understand the genetic makeup and impact on pharmacokinetics (PK) in the Taiwanese population, we analyzed the pharmacogenetic (PG) profile and demonstrated its effects on enzyme metabolism using indapamide as an example. A multiplex mass spectrometry method was used to examine the single nucleotide polymorphism (SNP) profile of eight major phases I and II metabolic enzymes in 1,038 Taiwanese subjects. A PG/PK study was conducted in 24 healthy subjects to investigate the possible effects of 28 SNPs on drug biotransformation. Among the genetic profile analyzed, eight SNPs from CYP2A6, CYP2C19, CYP2D6, CYP2E1, CYP3A5, and UGT2B7 showed higher variant frequencies than those previously reported in Caucasians or Africans. For instance, we observed 14.7% frequency of the SNP rs5031016 (I471T) from CYP2A6 in Taiwanese, whereas 0% variation was reported in Caucasians and Africans. The PG/PK study of indapamide demonstrated that the polymorphic SNPs CYP2C9 rs4918758 and CYP2C19 rs4244285 appeared to confer lowered enzyme activity, as indicated by increased C max (25% approximately 64%), increased area under the plasma level-time curves (30~76%), increased area under the time infinity (43% approximately 80%), and lower apparent clearance values than PK for wild-type indapamide. Our results reinforce the biochemical support of CYP2C19 in indapamide metabolism and identify a possible new participating enzyme CYP2C9. The PG/PK approach contributed toward understanding the genetic makeup of different ethnic groups and associations of enzymes in drug metabolism. It could be used to identify two genetic markers that enable to differentiate subjects with varied PK outcomes of indapamide. Twit Text FOAVip Genetic polymorphisms of metabolic enzymes and the pharmacokinetics of indapamide in Taiwanese subjects ????AAPS J http://www.kidney.de/pget.php?&tw=1&pmid=24357089 #FOAvip Twit Text # Free Paper on # # # # # LINK http://www.kidney.de/pget.php?&tw=1&pmid=24357089 #FOAvip English Wikipedia <ref>{{Cite pmid|24357089}}</ref> Genetic polymorphisms of metabolic enzymes and the pharmacokinetics of indapamide in Taiwanese subjects #MMPMID24357089 Wang TH; Hsiong CH; Ho HT; Shih TY; Yen SJ; Wang HH; Wu JY; Kuo BP; Chen YT; Ho ST; Hu OY AAPS J 2014[Mar]; 16 (2): 206-13 PMID24357089show ga To understand the genetic makeup and impact on pharmacokinetics (PK) in the Taiwanese population, we analyzed the pharmacogenetic (PG) profile and demonstrated its effects on enzyme metabolism using indapamide as an example. A multiplex mass spectrometry method was used to examine the single nucleotide polymorphism (SNP) profile of eight major phases I and II metabolic enzymes in 1,038 Taiwanese subjects. A PG/PK study was conducted in 24 healthy subjects to investigate the possible effects of 28 SNPs on drug biotransformation. Among the genetic profile analyzed, eight SNPs from CYP2A6, CYP2C19, CYP2D6, CYP2E1, CYP3A5, and UGT2B7 showed higher variant frequencies than those previously reported in Caucasians or Africans. For instance, we observed 14.7% frequency of the SNP rs5031016 (I471T) from CYP2A6 in Taiwanese, whereas 0% variation was reported in Caucasians and Africans. The PG/PK study of indapamide demonstrated that the polymorphic SNPs CYP2C9 rs4918758 and CYP2C19 rs4244285 appeared to confer lowered enzyme activity, as indicated by increased C max (25% approximately 64%), increased area under the plasma level-time curves (30~76%), increased area under the time infinity (43% approximately 80%), and lower apparent clearance values than PK for wild-type indapamide. Our results reinforce the biochemical support of CYP2C19 in indapamide metabolism and identify a possible new participating enzyme CYP2C9. The PG/PK approach contributed toward understanding the genetic makeup of different ethnic groups and associations of enzymes in drug metabolism. It could be used to identify two genetic markers that enable to differentiate subjects with varied PK outcomes of indapamide. |*Polymorphism, Single Nucleotide[MESH] |Chromatography, High Pressure Liquid[MESH] |Cytochrome P-450 Enzyme System/*metabolism[MESH] |Gene Frequency[MESH] |Glucuronosyltransferase/*metabolism[MESH] |Healthy Volunteers[MESH] |Humans[MESH] |Indapamide/*pharmacokinetics[MESH] |Linkage Disequilibrium[MESH] |Mass Spectrometry[MESH]Genetic polymorphisms of metabolic enzymes and the pharmacokinetics of(epmc).pdf DeepDyve Pubget Overpricing