2010
DOI: 10.1038/tpj.2010.42
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Effects of diltiazem on pharmacokinetics of tacrolimus in relation to CYP3A5 genotype status in renal recipients: from retrospective to prospective

Abstract: The impact of CYP3A5*3, a CYP3A5 nonexpresser genotype, on inhibitory effects of diltiazem on tacrolimus metabolism has not been assessed. In retrospective study, when coadministered with diltiazem, mean increments in dose-adjusted C 0D7 , C max and AUC 0-12 h for tacrolimus were larger in CYP3A5 expressers than in CYP3A5 nonexpressers (48.7 vs 3.7%, 31.7 vs 17.2% and 38.2 vs 18.5%, respectively). Subsequently, a prospective study was carried out, patients were randomized to algorithm-predicted dosing or stand… Show more

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Cited by 49 publications
(50 citation statements)
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References 37 publications
(36 reference statements)
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“…Multiple CCBs were used in our study and we did not collect the specific CCB prescribed. The CCB, diltiazem, is a well-known potent inhibitor of the CYP3A enzyme and decreases tacrolimus CL/F [48,49]. Other CCBs (such as amlodipine) are not potent inhibitors of CYP3A [50].…”
Section: Figurementioning
confidence: 99%
“…Multiple CCBs were used in our study and we did not collect the specific CCB prescribed. The CCB, diltiazem, is a well-known potent inhibitor of the CYP3A enzyme and decreases tacrolimus CL/F [48,49]. Other CCBs (such as amlodipine) are not potent inhibitors of CYP3A [50].…”
Section: Figurementioning
confidence: 99%
“…133 The calcium channel blocker diltiazem has been used as a tacrolimussparing agent due to its effect as an inhibitor of tacrolimus metabolism. 134,135 Evidence in kidney transplant patients suggests that CYP3A5 expressers are more susceptible to diltiazeminduced tacrolimus metabolism than nonexpressers. 135 The drugs that are most frequently responsible for interactions with tacrolimus in the liver transplant population are other immunosuppressants, antifungals, macrolide antimicrobials and the protease inhibitors commonly used in chronic hepatitis C virus (HCV) and human immunodeficiency virus (HIV).…”
Section: Highly Modifiable Contributors To Variabilitymentioning
confidence: 99%
“…134,135 Evidence in kidney transplant patients suggests that CYP3A5 expressers are more susceptible to diltiazeminduced tacrolimus metabolism than nonexpressers. 135 The drugs that are most frequently responsible for interactions with tacrolimus in the liver transplant population are other immunosuppressants, antifungals, macrolide antimicrobials and the protease inhibitors commonly used in chronic hepatitis C virus (HCV) and human immunodeficiency virus (HIV). 133 Regarding immunosuppressive drugs, anti-IL2 receptor agents and corticosteroids are able to decrease and increase the tacrolimus dose requirement, respectively, but the interaction is usually mild and without clinical consequences.…”
Section: Highly Modifiable Contributors To Variabilitymentioning
confidence: 99%
“…The POR rs1057868-rs2868177 GC-GT diplotype is associated with high tacrolimus concentrations in early post-renal transplant recipients nonfunctional splicing-defect in CYP3A5*3 allele (rs776746; 6985A>G) [5][6][7] . CYP3A5*3/*3 carriers (CYP3A5 function deficient, denominated as CYP3A5 nonexpressers) require a lower dose of tacrolimus to reach target concentrations compared with CYP3A5*1 allele carriers (CYP3A5 expressers).…”
Section: Original Articlementioning
confidence: 99%
“…Total genomic DNA was extracted from the peripheral leukocytes according to a previously described method [18] . CYP3A5*3 was determined by using published polymerase chain reaction restriction-fragment length polymorphism (PCR-RFLP) methods [5,19] . 6 POR SNPs were detected by Agena Bioscience MassARRAY ® system (Agena Bioscience, San Diego, CA, USA).…”
Section: Dna Extraction and Genotypingmentioning
confidence: 99%