CYP3A5 Polymorphism affects the increase in CYP3A activity after living Kidney transplantation in patients with end stage renal disease

Suzuki, Yosuke; Fujioka, Takashi; Sato, Fuminori; Matsumoto, K.; Muraya, Nanako; Tanaka, Ryota; Sato, Yukie; Ohno, Keiko; Mimata, Hiromitsu; Kishino, Satoshi

doi:10.1016/j.clinthera.2015.05.152

Cited by 7 publications

(12 citation statements)

References 24 publications

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“…The gradual increase in 4bOHC concentration with increasing time after transplantation coincides with findings in Japanese kidney transplant recipients, in which a 30%-50% increase in 4bOHC concentration was found on days 90 and 180 after transplantation compared with pretransplant 4bOHC concentration (Suzuki et al, 2013(Suzuki et al, , 2015. Furthermore, in vitro studies of rat hepatocytes incubated with serum from chronic renal failure patients reported a reduction in CYP3A activity and enzyme expression before, but not after, transplantation (Michaud et al, 2005).…”

Section: Discussionsupporting

confidence: 81%

“…Suzuki et al (2015) reported identical pretransplantation 4bOHC levels in CYP3A5*1 carriers and noncarriers, with a mean concentration of 38 ng/ml. They further reported a post-transplantation increase in 4bOHC concentration only among CYP3A5*1 carriers, and not among CYP3A5*3/*3 homozygotes (Suzuki et al, 2015). We found no difference in the post-transplantation increase in 4bOHC concentration when comparing CYP3A4*22 carriers, CYP3A4*1/*1 and CYP3A5*3/*3 homozygotes, and CYP3A5*1 carriers, indicating a recovery of CYP3A activity independent of genotype.…”

Section: Discussionmentioning

confidence: 83%

“…It is also possible that nongenetic factors, such as inflammation and uremic toxins, mask the effects of CYP3A4 genotype on CYP3A phenotype in this population (Morgan, 1997;Suzuki et al, 2014). Suzuki et al (2015) reported identical pretransplantation 4bOHC levels in CYP3A5*1 carriers and noncarriers, with a mean concentration of 38 ng/ml. They further reported a post-transplantation increase in 4bOHC concentration only among CYP3A5*1 carriers, and not among CYP3A5*3/*3 homozygotes (Suzuki et al, 2015).…”

Section: Discussionmentioning

confidence: 93%

“…Study results are conflicting, however, regarding change in CYP3A phenotype after kidney transplantation, with reports of increased 4bOHC concentration (Suzuki et al, 2013) and decreased midazolam clearance (de Jonge et al, 2015). Furthermore, Suzuki et al (2015) reported that post-transplant change in 4bOHC concentration was dependent on CYP3A5 genotype since only CYP3A5*1 carriersand not CYP3A5*3/*3 homozygotes-experienced increased enzyme activity after transplantation. Thus, further elucidation of CYP3Ametabolizing status after kidney transplantation is needed.…”

Section: Introductionmentioning

confidence: 99%

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Recovery of CYP3A Phenotype after Kidney Transplantation

et al. 2017

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End-stage renal disease impairs drug metabolism via cytochrome P450 CYP3A; however, it is unclear whether CYP3A activity recovers after kidney transplantation. Therefore, the aim of this study was to evaluate the change in CYP3A activity measured as 4-hydroxycholesterol (4OHC) concentration after kidney transplantation. In total, data from 58 renal transplant recipients with 550 prospective 4OHC measurements were included in the study. One sample per patient was collected before transplantation, and 2-12 samples per patient were collected 1-82 days after transplantation. The measured pretransplant 4OHC concentrations ranged by >7-fold, with a median value of 22.8 ng/ml. Linear mixed-model analysis identified a 0.16-ng/ml increase in 4OHC concentration per day after transplantation ( < 0.001), indicating a regain in CYP3A activity. Increasing estimated glomerular filtration rate after transplantation was associated with increasing 4OHC concentration ( < 0.001), supporting that CYP3A activity increases with recovering uremia. In conclusion, this study indicates that CYP3A activity is regained subsequent to kidney transplantation.

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Section: Discussionsupporting

confidence: 81%

Section: Discussionmentioning

confidence: 83%

Section: Discussionmentioning

confidence: 93%

Section: Introductionmentioning

confidence: 99%

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Recovery of CYP3A Phenotype after Kidney Transplantation

et al. 2017

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“…Pharmacokinetic parameters of CYP2D6 and CYP3A4/5 model drugs that have clinical CKD study reports CYP3A4/5, and renal excretion can contribute to the clearance of model drugs. Another possible source of variability is different effects of CKD on CYP3A4 and CYP3A5 21. To further evaluate CYP2D6 and CYP3A4/5 activity changes quantitatively, it is imperative to have a good understanding of the detailed elimination mechanisms of each model drug.…”

mentioning

confidence: 99%

Systematic and quantitative assessment of the effect of chronic kidney disease on CYP2D6 and CYP3A4/5

Yoshida

Sun

Zhang

et al. 2016

Clin Pharma and Therapeutics

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Recent reviews suggest that chronic kidney disease (CKD) can affect the pharmacokinetics of nonrenally eliminated drugs, but the impact of CKD on individual elimination pathways has not been systematically evaluated. In this study we developed a comprehensive dataset of the effect of CKD on the pharmacokinetics of CYP2D6‐ and CYP3A4/5‐metabolized drugs. Drugs for evaluation were selected based on clinical drug–drug interaction (CYP3A4/5 and CYP2D6) and pharmacogenetic (CYP2D6) studies. Information from dedicated CKD studies was available for 13 and 18 of the CYP2D6 and CYP3A4/5 model drugs, respectively. Analysis of these data suggested that CYP2D6‐mediated clearance is generally decreased in parallel with the severity of CKD. There was no apparent relationship between the severity of CKD and CYP3A4/5‐mediated clearance. The observed elimination‐route dependency in CKD effects between CYP2D6 and CYP3A4/5 may inform the need to conduct clinical CKD studies with nonrenally eliminated drugs for optimal use of drugs in patients with CKD.

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