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Individualization of tacrolimus dosage basing on cytochrome P450 3A5 polymorphism – a prospective, randomized, controlled study
Author(s) -
Chen SiYang,
Li JiaLi,
Meng FanHang,
Wang XueDing,
Liu Tao,
Li Jun,
Liu LongShan,
Fu Qian,
Huang Min,
Wang ChangXi
Publication year - 2013
Publication title -
clinical transplantation
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.918
H-Index - 76
eISSN - 1399-0012
pISSN - 0902-0063
DOI - 10.1111/ctr.12101
Subject(s) - tacrolimus , diltiazem , pharmacokinetics , dosing , medicine , cyp3a5 , pharmacology , transplantation , genotype , biology , biochemistry , gene , calcium
We investigated how cytochrome P450 ( CYP ) 3A5 polymorphism affects pharmacokinetics of tacrolimus and its interaction with diltiazem in Chinese kidney transplant recipients. Sixty‐two CYP 3A5 expressers and 58 non‐expressers were, respectively, randomized to receive diltiazem supplement or not. Their pharmacokinetic profiles were acquired on 14th day, sixth month, and 18th month post‐transplant and compared among groups. A dosing equation was fit based on above data with CYP 3A5 genotype and diltiazem co‐administration as variables. Then, necessary initial doses with or without diltiazem were calculated and used in 11 CYP 3A5 expressers, respectively, when another 11 expressers received routine doses as control. Trough concentration was measured on the third‐day post‐transplant and patients failed to reach target range were presented in percentage. These two parameters were compared among three groups. Patients were followed up until June 2010, kidney function, biopsy‐proved acute rejection, and other adverse events were monitored. Results showed that CYP 3A5 expressers needed more tacrolimus to reach therapeutic concentration window and were more susceptible to diltiazem‐induced concentration increase than CYP 3A5 non‐expressers. CYP 3A5 polymorphism‐guided dosing equation helped to determine appropriate initial doses of tacrolimus in individuals. In conclusion, CYP 3A5 polymorphism profoundly influences pharmacokinetics of tacrolimus and helps to individualize tacrolimus dose.