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Switching Immunosuppression From Cyclosporine to Tacrolimus in Kidney Transplant Recipients Based on CYP3A5 Genotyping

Wang, Xuebin, MS*; Yang, Yunyun, MS*; Liu, Zhengyue, BS*; Xiao, Chengwu, MD; Gao, Lihong, PhD*; Zhang, Wenjing, MS*; Zhang, Wenwen, BS*; Wang, Zhuo, PhD*

doi: 10.1097/FTD.0000000000000579
Short Communication

Background: Kidney transplant recipients on long-term cyclosporine (CsA) therapy may develop multiple adverse drug events, and immunosuppression conversion from CsA to tacrolimus (Tac) is an option. Genetic variations, especially cytochrome P450 (CYP) 3A5*3, affects Tac dosing. However, little information is available to guide the conversion with regards to patients' pharmacogenomics. We aimed to investigate whether CYP3A5, CYP3A4, and ABCB1 genotyping could contribute to a more precise and individualized initial dosing of Tac at the time of immunosuppressant conversion.

Methods: Genotypes of 5 candidate genes (CYP3A5*3, CYP3A4*1G, ABCB1C1236T, ABCB1C3435T, and ABCB1G2677T/A) were investigated by polymerase chain reaction and restriction fragment-length polymorphism methods in 46 adult kidney transplant recipients requiring immunosuppressant conversion from CsA to TAC. Associations between these functional genetic polymorphisms and the dose-adjusted trough concentrations of CsA and Tac were evaluated, retrospectively.

Results: Based on the linear regression analysis, CYP3A5 expressers (*1/*1 and *1/*3) had lower Tac dose-adjusted trough concentrations on days 7, 14, 21, and 28, and they required 1.40- to 1.75-fold higher daily dose to reach the target concentration compared with nonexpressers (*3/*3) on day 28 [0.07 (0.06–0.09) mg/kg/d versus 0.05 (0.02–0.06) mg/kg/d, P = 0.001]. CYP3A4*1G or ABCB1 genetic polymorphisms had no effect on the Tac dose-adjusted trough concentrations.

Conclusions: Our preliminary study supports the use of CYP3A5 genotyping to guide the initial dosing of Tac when converting the immunosuppression therapy from CsA to Tac.

Departments of *Pharmacy; and

Urinary Surgery, Shanghai Changhai Hospital, Second Military Medical University, Shanghai, China.

Correspondence: Zhuo Wang, PhD, Department of Pharmacy, Shanghai Changhai Hospital, Second Military Medical University, Shanghai 200433, China (e-mail: wztgyx223@163.com).

Supported by Shanghai Municipal Commission of Health and Family Flanning-Construction of clinical pharmacy service system (2016ZB0303), scientific research project of hospital pharmacy of Shanghai Pharmaceutical Association (2017-YY-02-13), and military construction of the national key clinical specialist-clinical pharmacy.

X. Wang, Y. Yang, and Z. Liu have contributed equally to this work.

The authors declare no conflict of interest.

Received April 17, 2018

Accepted October 04, 2018

Copyright © 2019 Wolters Kluwer Health, Inc. All rights reserved.