The Influence of Pharmacogenetics on the Time to Achieve Target Tacrolimus Concentrations after Kidney Transplantation

@article{Macphee2004TheIO,
  title={The Influence of Pharmacogenetics on the Time to Achieve Target Tacrolimus Concentrations after Kidney Transplantation},
  author={I Macphee and Salim Fredericks and Tracy Tai and Petros Syrris and Nicholas D. Carter and Atholl Johnston and Lawrence Goldberg and David W Holt},
  journal={American Journal of Transplantation},
  year={2004},
  volume={4}
}
Previously, we reported that, at 3 months after renal transplantation, individuals with CYP3AP1 genotype CYP3AP1*1 (linked to CYP3A5*1 and strongly associated with expression of CYP3A5) required twofold higher doses of tacrolimus to achieve target blood concentrations than individuals with the genotype CYP3AP1*3/*3 (CYP3A5 nonexpressors). This study assesses the relationship between concentration‐controlled dosing during the early period after transplantation, the time to achieve target… Expand
Factors affecting the long-term response to tacrolimus in renal transplant patients: Pharmacokinetic and pharmacogenetic approach
TLDR
It is proved that CYP3A5*1 carriers need higher tacrolimus dose than CYP5*3 homozygotes to achieve the target blood concentration. Expand
CYP3A5 genotype is not associated with a higher risk of acute rejection in tacrolimus-treated renal transplant recipients
TLDR
It is concluded that patients expressing CYP3A5 need more tacrolimus to reach target concentrations and have a lower tac rolimus exposure shortly after transplantation, but this delay in reaching target concentrations did not result in an increased incidence of early BPAR and therefore, genotyping for CYP 3A5 is unlikely to improve short-term transplantation outcome. Expand
Impact of CYP3A4*22 Allele on Tacrolimus Pharmacokinetics in Early Period After Renal Transplantation: Toward Updated Genotype-Based Dosage Guidelines
TLDR
This study confirms the decreased CYP3A4 activity toward Tac for CYP 3A4*22 carriers early after transplantation and provides evidence for refining genotype-based dosage by adding the CYP2A5*3 genotype information to the CYp3A5-3 allelic status. Expand
Influence of CYP3A5 genetic polymorphism on tacrolimus daily dose requirements and acute rejection in renal graft recipients.
TLDR
CYP3A5 genetic polymorphism appeared in this study to affect tacrolimus daily dose requirements and transplantation outcome and Screening for this single nucleotide polymorphism before the transplantation might be helpful for the selection of adequate initial daily dose and to achieve the desired immunosuppression. Expand
Value of CYP3A5 genotyping on determining initial dosages of tacrolimus for Chinese renal transplant recipients.
TLDR
Initial tacrolimus dosage selection based on CYP3A5 genotyping can improve drug blood levels in the early stage following renal transplantation, and CYP 3A5 polymorphism plays an important role in influencing tacolimus blood levels. Expand
Impact of CYP3A5 polymorphism on trough concentrations and outcomes of tacrolimus minimization during the early period after kidney transplantation
TLDR
Although CYP3A5 polymorphism significantly influenced the tacrolimus dose required to achieve the target concentration, the impact of CYP2A4*1 allele carriers on BPAR was not observed in this study. Expand
Influence of the Cyp3a5 genotype on tacrolimus pharmacokinetics and pharmacodynamics in young kidney transplant recipients
TLDR
It is concluded that a pre‐emptive CYP3A5 pharmacogenetic screening could contribute to better individualization of TAC therapy and be correlated with one of the most common TAC side‐effects suggesting a possible influence of CYP 3A5 polymorphism on TAC pharmacodynamics. Expand
Explaining Variability in Tacrolimus Pharmacokinetics to Optimize Early Exposure in Adult Kidney Transplant Recipients
TLDR
An integrated analysis shows that adult renal transplant recipients with the CYP3A5*1/*3 genotype require a 1.5 times higher, fixed, starting dose compared with CYP5*3/*3 to reach the predefined target exposure early after transplantation. Expand
Combined effects of CYP3A5*1, POR*28, and CYP3A4*22 single nucleotide polymorphisms on early concentration-controlled tacrolimus exposure in de-novo renal recipients
TLDR
Combining the CYP3A5*1, POR*28 and CYP 3A4*22 genotypes allows partial differentiation of early tacrolimus dose requirements and the time to reach therapeutic target concentrations after transplantation, but without obvious clinical implications. Expand
CYP3A5 *1 Allele: Impacts on Early Acute Rejection and Graft Function in Tacrolimus-Based Renal Transplant Recipients
TLDR
The significant effects of CYP3A5 polymorphism on the achievement of target tacrolimus trough levels and the development of acute rejection in early period after transplantation and consequent renal allograft function are confirmed. Expand
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Determination of CYP3A5 genotype is predictive of the dose of tacrolimus in renal transplant recipients and may help to determine the initial daily dose needed by individual patients for adequate immunosuppression without excess nephrotoxicity. Expand
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