Genetic polymorphisms of CYP3A5 genes and concentration of the cyclosporine and tacrolimus

Zhao, Yongxiang; Song, Muguo; Guan, Dawei; Bi, Shulutko; Meng, Jinxiu; Li, Q.; Wang, W.

doi:10.1016/j.transproceed.2005.01.077

Cited by 83 publications

(34 citation statements)

References 11 publications

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“…This type of inconsistency is common, and does not appear to be influenced by race. Indeed, three different studies, all with around 100 Chinese renal recipients, found that, respectively, the * 3 allele was associated with higher dose-adjusted trough concentrations, lower dose-adjusted trough concentrations, and not associated with trough concentrations at all [194-196], exemplifying the type of conflicting evidence seen in these pharmacokinetic studies. Indeed, the study finding lower dose-adjusted trough concentrations [196] is particularly confusing, as the CYP3A5 * 3 allele results in a nonfunctional protein [115], implying that dose-adjusted trough concentrations should be higher in * 3 allele carriers.…”

Section: Influence On Cyclosporine Pharmacokinetics and Pharmacodynamicsmentioning

confidence: 99%

PharmGKB summary

Barbarino¹,

Staatz²,

Venkataramanan³

et al. 2013

Pharmacogenetics and Genomics

205

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Section: Influence On Cyclosporine Pharmacokinetics and Pharmacodynamicsmentioning

confidence: 99%

PharmGKB summary

Barbarino¹,

Staatz²,

Venkataramanan³

et al. 2013

Pharmacogenetics and Genomics

205

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“…Tacrolimus trough concentrations are routinely monitored after transplantation, and the dose is appropriately adjusted. Despite the well-established association of the CYP3A5 genotype with clearance rate and trough levels [23–31], it has not been consistently shown to be associated with the risk of acute organ rejection. It has also not yet been shown that genotype-guided dosing leads to improved clinical outcomes.…”

Section: Variant-drug Associationsmentioning

confidence: 99%

PharmGKB summary

Lamba

Hebert

Schuetz

et al. 2012

Pharmacogenetics and Genomics

135

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“…CYP3A5 gene is expressed in a limited number of individuals. When it is expressed, it may count for the 50% of the total hepatic CYP3A protein 5,14.…”

Section: Introductionmentioning

confidence: 99%

Factors affecting the long-term response to tacrolimus in renal transplant patients: Pharmacokinetic and pharmacogenetic approach

Katsakiori¹,

Papapetrou²,

Sakellaropoulos³

et al. 2010

Int. J. Med. Sci.

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Background: The aim of our study was to determine the impact of CYP3A5*1 and CYP3A5*3 on the kinetics of tacrolimus in renal transplant recipients.Material and methods: Forty kidney recipients were selected to participate. Maintenance scheme consisted of tacrolimus, a purine inhibitor and a steroid. CYP3A5 genotyping was performed with PCR and RFLP. Pharmacokinetic model was developed with Linear Regression and General Linear Model repeated measures approach. The impact of sex, CYP3A5*1 allele, age at transplantation, hepatic and renal function on tacrolimus kinetics was examined.Results: The frequency of CYP3A5*3/*3 and CYP3A5*1/*3 genotype was 35/40 and 5/40, respectively. No CYP3A5*1/*1 was detected. CYP3A5*1 variant was associated with significant lower TAC dose adjusted concentration at 3, 6, 12 and 36 months after transplantation. Hepatic and renal function showed a significant effect on tacrolimus dose adjusted concentration 3 months after transplantation (p=0.000 and 0.028, respectively). Sex did not show a significant impact on tacrolimus kinetics. Carriers of CYP3A5*1 allele had lower predicted measures for tacrolimus dose adjusted concentration and higher predicted measures for volume of distribution.Conclusion: We proved that CYP3A5*1 carriers need higher tacrolimus dose than CYP3A5*3 homozygotes to achieve the target blood concentration.

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Genetic polymorphisms of CYP3A5 genes and concentration of the cyclosporine and tacrolimus

Cited by 83 publications

References 11 publications

PharmGKB summary

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Factors affecting the long-term response to tacrolimus in renal transplant patients: Pharmacokinetic and pharmacogenetic approach

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