Preprint Article Version 1 Preserved in Portico This version is not peer-reviewed

Effect of CYP3A5 Polymorphism on Liver Function and Tacrolimus Pharmacokinetics after Conversion to a Once-Daily Tacrolimus Formulation in Stable Liver Transplant Patients

Version 1 : Received: 1 August 2020 / Approved: 3 August 2020 / Online: 3 August 2020 (01:11:59 CEST)

A peer-reviewed article of this Preprint also exists.

Kim, J.M.; Ryu, J.H.; Lee, K.-W.; Hong, S.K.; Yang, K.; Choi, G.-S.; Kim, Y.-A.; Lee, J.-Y.; Yi, N.-J.; Kwon, C.H.D.; Chu, C.W.; Suh, K.-S.; Joh, J.-W. Effect of CYP3A5 on the Once-Daily Tacrolimus Conversion in Stable Liver Transplant Patients. J. Clin. Med. 2020, 9, 2897. Kim, J.M.; Ryu, J.H.; Lee, K.-W.; Hong, S.K.; Yang, K.; Choi, G.-S.; Kim, Y.-A.; Lee, J.-Y.; Yi, N.-J.; Kwon, C.H.D.; Chu, C.W.; Suh, K.-S.; Joh, J.-W. Effect of CYP3A5 on the Once-Daily Tacrolimus Conversion in Stable Liver Transplant Patients. J. Clin. Med. 2020, 9, 2897.

Journal reference: J. Clin. Med. 2020, 9, 2897
DOI: 10.3390/jcm9092897

Abstract

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. 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). 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. 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.

Subject Areas

Pharmacokinetics; Immunosuppression; Tacrolimus

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