Preprint Article Version 1 Preserved in Portico This version is not peer-reviewed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

Jong Man Kim
ORCID logo ,
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 David Kwon
,
Chong Woo Chu
,
Kyung-Suk Suh
,
Jae-Won Joh
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.

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.

Keywords

Pharmacokinetics; Immunosuppression; Tacrolimus

Subject

Medicine and Pharmacology, Gastroenterology and Hepatology

Copyright: This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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