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.
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.
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.
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: firstname.lastname@example.org).
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