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Capability of utilizing CYP3A5 polymorphisms to predict therapeutic dosage of tacrolimus at early stage post-renal transplantation.

Niioka T, Kagaya H, Saito M, Inoue T, Numakura K, Habuchi T, Satoh S, Miura M - Int J Mol Sci (2015)

Bottom Line: The contribution of genetic factors (CYP3A5*1 or *3) for tacrolimus dosing showed increased variation from Day 14 to Day 28 after transplantation: 7.2%, 18.4% and 19.5% on Days 14, 21 and 28, respectively.The influence of CYP3A5 polymorphisms on the tacrolimus maintenance dosage became evident after Day 14 post-transplantation, although the tacrolimus dosage was determined based only on patient body weight for the first three days after surgery.Tacrolimus dosage starting with the initial administration should be individualized using the CYP3A5 genotype information.

View Article: PubMed Central - PubMed

Affiliation: Department of Pharmacy, Akita University Hospital, 1-1-1 Hondo, Akita 010-8543, Japan. tniio-hki@umin.ac.jp.

ABSTRACT
While CYP3A5 polymorphisms are used to predict the initial dosage of tacrolimus therapy, the predictive capability of genetic information for dosing at early stage post-renal transplantation is unknown. We investigated the influence of polymorphisms over time. An initial oral dose of modified-release once-daily tacrolimus formulation (0.20 mg/kg) was administered to 50 Japanese renal transplant patients every 24 h. Stepwise multiple linear regression analysis for tacrolimus dosing was performed each week to determine the effect of patient clinical characteristics. The dose-adjusted trough concentration was approximately 70% higher for patients with the CYP3A5*3/*3 than patients with the CYP3A5*1 allele before the second pre-transplantation tacrolimus dose (0.97 (0.78-1.17) vs. 0.59 (0.45-0.87) ng/mL/mg; p < 0.001). The contribution of genetic factors (CYP3A5*1 or *3) for tacrolimus dosing showed increased variation from Day 14 to Day 28 after transplantation: 7.2%, 18.4% and 19.5% on Days 14, 21 and 28, respectively. The influence of CYP3A5 polymorphisms on the tacrolimus maintenance dosage became evident after Day 14 post-transplantation, although the tacrolimus dosage was determined based only on patient body weight for the first three days after surgery. Tacrolimus dosage starting with the initial administration should be individualized using the CYP3A5 genotype information.

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Comparison of achievement rates from the initial C0h to the target range (target C0h ± 20%) between CYP3A5 genotypes at each stage after renal transplantation. White columns, lower than the target range; black columns, within the target range; gray columns; more than the target range. EM (*1/*1 + *1/*3), n = 17; PM (*3/*3), n = 33.
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ijms-16-01840-f003: Comparison of achievement rates from the initial C0h to the target range (target C0h ± 20%) between CYP3A5 genotypes at each stage after renal transplantation. White columns, lower than the target range; black columns, within the target range; gray columns; more than the target range. EM (*1/*1 + *1/*3), n = 17; PM (*3/*3), n = 33.

Mentions: The achievement rates from the initial C0h to the target range (target level ± 20%) were lower for CYP3A5 EM than PM patients on Days 7 and 14 (11.8% vs. 51.5%, p = 0.011; and 5.9% vs. 54.5%, p = 0.001) (Figure 3). In particular, the rates lower than the target range on Days 7 and 14 were high in the CYP3A5 EM group (76.5% and 88.2%). On the other hand, the achievement rates for the CYP3A5 PM group were stable at more than 50% at the early stage post-transplantation (Figure 3).


Capability of utilizing CYP3A5 polymorphisms to predict therapeutic dosage of tacrolimus at early stage post-renal transplantation.

Niioka T, Kagaya H, Saito M, Inoue T, Numakura K, Habuchi T, Satoh S, Miura M - Int J Mol Sci (2015)

Comparison of achievement rates from the initial C0h to the target range (target C0h ± 20%) between CYP3A5 genotypes at each stage after renal transplantation. White columns, lower than the target range; black columns, within the target range; gray columns; more than the target range. EM (*1/*1 + *1/*3), n = 17; PM (*3/*3), n = 33.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4307337&req=5

ijms-16-01840-f003: Comparison of achievement rates from the initial C0h to the target range (target C0h ± 20%) between CYP3A5 genotypes at each stage after renal transplantation. White columns, lower than the target range; black columns, within the target range; gray columns; more than the target range. EM (*1/*1 + *1/*3), n = 17; PM (*3/*3), n = 33.
Mentions: The achievement rates from the initial C0h to the target range (target level ± 20%) were lower for CYP3A5 EM than PM patients on Days 7 and 14 (11.8% vs. 51.5%, p = 0.011; and 5.9% vs. 54.5%, p = 0.001) (Figure 3). In particular, the rates lower than the target range on Days 7 and 14 were high in the CYP3A5 EM group (76.5% and 88.2%). On the other hand, the achievement rates for the CYP3A5 PM group were stable at more than 50% at the early stage post-transplantation (Figure 3).

Bottom Line: The contribution of genetic factors (CYP3A5*1 or *3) for tacrolimus dosing showed increased variation from Day 14 to Day 28 after transplantation: 7.2%, 18.4% and 19.5% on Days 14, 21 and 28, respectively.The influence of CYP3A5 polymorphisms on the tacrolimus maintenance dosage became evident after Day 14 post-transplantation, although the tacrolimus dosage was determined based only on patient body weight for the first three days after surgery.Tacrolimus dosage starting with the initial administration should be individualized using the CYP3A5 genotype information.

View Article: PubMed Central - PubMed

Affiliation: Department of Pharmacy, Akita University Hospital, 1-1-1 Hondo, Akita 010-8543, Japan. tniio-hki@umin.ac.jp.

ABSTRACT
While CYP3A5 polymorphisms are used to predict the initial dosage of tacrolimus therapy, the predictive capability of genetic information for dosing at early stage post-renal transplantation is unknown. We investigated the influence of polymorphisms over time. An initial oral dose of modified-release once-daily tacrolimus formulation (0.20 mg/kg) was administered to 50 Japanese renal transplant patients every 24 h. Stepwise multiple linear regression analysis for tacrolimus dosing was performed each week to determine the effect of patient clinical characteristics. The dose-adjusted trough concentration was approximately 70% higher for patients with the CYP3A5*3/*3 than patients with the CYP3A5*1 allele before the second pre-transplantation tacrolimus dose (0.97 (0.78-1.17) vs. 0.59 (0.45-0.87) ng/mL/mg; p < 0.001). The contribution of genetic factors (CYP3A5*1 or *3) for tacrolimus dosing showed increased variation from Day 14 to Day 28 after transplantation: 7.2%, 18.4% and 19.5% on Days 14, 21 and 28, respectively. The influence of CYP3A5 polymorphisms on the tacrolimus maintenance dosage became evident after Day 14 post-transplantation, although the tacrolimus dosage was determined based only on patient body weight for the first three days after surgery. Tacrolimus dosage starting with the initial administration should be individualized using the CYP3A5 genotype information.

Show MeSH
Related in: MedlinePlus