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Effect of CYP3A5 polymorphism on liver function and tacrolimus pharmacokinetics after conversion to a once-daily tacrolimus formulation in stable liver transplant patients
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  • Jong Man Kim,
  • Je Ho Ryu,
  • Kwang-Woong Lee,
  • Suk Kyun Hong,
  • Kwangho Yang,
  • Gyu-Seong Choi,
  • Young-ae Kim,
  • Ju-Yeun Lee,
  • Nam-Joon Yi,
  • Choon Hyuck Kwon,
  • Chong Woo Chu,
  • Kyung-Suk Suh,
  • Jae-Won Joh
Jong Man Kim
Samsung Medical Center
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Je Ho Ryu
Pusan National University Yangsan Hospital
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Kwang-Woong Lee
Seoul National University College of Medicine
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Suk Kyun Hong
Seoul National University College of Medicine
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Kwangho Yang
Pusan National University Yangsan Hospital
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Gyu-Seong Choi
Samsung Medical Center
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Young-ae Kim
Seoul National University Hospital
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Ju-Yeun Lee
Seoul National University
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Nam-Joon Yi
Seoul National University College of Medicine
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Choon Hyuck Kwon
Cleveland Clinic
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Chong Woo Chu
Good Gangan Hospital
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Kyung-Suk Suh
Seoul National University College of Medicine
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Jae-Won Joh
Samsung Medical Center
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Abstract

Aim: To analyze the effects of CYP3A5 polymorphism on liver function after LT and to characterize the pharmacokinetics of tacrolimus after conversion from a twice-daily regimen to a once-daily extended-release formulation. Methods: A prospective open-label study included 60 stable liver transplant recipients who underwent 1:1 conversion from twice-daily tacrolimus to once-daily tacrolimus. All participants were genotyped for CYP3A5 polymorphism. The study was registered at ClinicalTrials.gov (NCT 02882113). Results: Twenty-eight patients were enrolled in the CYP3A5 expressor group and 32 in the non-expressor group. Although there was no statistical difference, incidence of liver dysfunction was higher in the expressor group than in the non-expressor group when converted to once-daily extended-release tacrolimus (P=0.088). No biopsy-proven acute rejection, graft failure, and mortality were observed in either group. The decrease in dose-adjusted trough level (- 42.9% vs. - 26.1%) and dose/kg-adjusted trough level of tacrolimus (- 40.0% vs. - 23.7%) was significantly greater in the expressor group than in the non-expressors after the conversion. The absorption of the tacrolimus in the non-expressor group was slower than in the expressors. In line with this observation, the AUC for once-daily tacrolimus correlated with Cmin in the non-expressors and Cmax in the expressors. Conclusions: Determination of CYP3A5 genotype in liver transplant recipients might be helpful in prediction of tacrolimus pharmacokinetics after conversion from a twice-daily regimen to a once-daily formulation.