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Abstract
Pharmaceutical Care and Research: 2018; 18(6):415-418
DOI: 10.5428/pcar20180605
Influence of pregnane X receptor genetic polymorphism on initial dosing of tacrolimus in renal transplant recipients converted from cyclosporine to tacrolimus
1. YANG YunYun(Department of Pharmacy,Changhai Hospital,Second Military Medical University,Shanghai 200433,China 13262246965@163.com)
2. CHEN JieXiu(Department of Pharmacy,Changhai Hospital,Second Military Medical University,Shanghai 200433,China chenjiexiu217@163.com)
3. WANG XueBin(Department of Pharmacy,Changhai Hospital,Second Military Medical University,Shanghai 200433,China )
4. HU XiDan(Department of Pharmacy,Changhai Hospital,Second Military Medical University,Shanghai 200433,China )
5. GAO LiHong(Department of Pharmacy,Changhai Hospital,Second Military Medical University,Shanghai 200433,China )
6. WANG Zhuo(Department of Pharmacy,Changhai Hospital,Second Military Medical University,Shanghai 200433,China wangzhuo088@163.com)
ABSTRACT  Objective: To investigate whether pregnane X receptor (PXR) genotyping could contribute to individual initial dosing of tacrolimus (TAC) at the time of conversion from cyclosporine (CsA) to TAC for renal transplant recipients.Methods: CYP3A5*3 and PXR genes were analyzed by PCR-RFLP method.Hardy-Weinberg equilibrium (HWE) and linkage disequilibrium (LD) pattern were tested by SHEsis software on line.One-way ANOVA test or Student Newman Keuls (M-W) test was used to evaluate the effects of CYP3A5*3 and PXR polymorphisms on the dose adjusted trough concentration (C0/D) of CsA and TAC retrospectively.Results: PXR(G7635A) genetic polymorphisms had no significant effect on CsA C0/D at day 0(P>0.05),but had an significant impact on TAC C0/D at days 7,14,21 and 28 after conversion (P<0.05).The recipients with AA genotype required 0.57-fold higher daily dose (D) to reach the target concentration of TAC C0 compared to AG and GG genotypes at day 28.However,for renal transplant patients with CYP3A5*3 GG genotype,PXR (G7635A) genetic polymorphisms had no effect on TAC C0/D after conversion.Conclusion: This study showed that PXR genetic polymorphism influenced the initial TAC dosing in renal transplant patients converted from CsA to TAC,which reguired further verification through enlarging the samples.
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Please cite this article as:
YANG YunYun,CHEN JieXiu,WANG XueBin,HU XiDan,GAO LiHong,WANG Zhuo,. Influence of pregnane X receptor genetic polymorphism on initial dosing of tacrolimus in renal transplant recipients converted from cyclosporine to tacrolimus[J]. Pharmaceutical Care and Research / yao xue fu wu yu yan jiu. 2018; 18(6): 415-418.
References:
1. Franke G H,Trampenau C,Reimer J,et al.Switching from cyclosporine to tacrolimus leads to improved disease-specific quality of life in patients after kidney transplantation[J].Transplant Proc,2006,38(5):1293-1294.
2. Lancia P,Aurich B,Ha P,et al.Adverse events under tacrolimus and cyclosporine in the first 3 years post-renal transplantation in children[J].Clin Drug Investig,2018,38(2):157-171.
3. Halloran P F.Immunosuppressive drugs for kidney transplantation[J].N Engl J Med,2004,351(26):2715-2729.
4. Thirumaran R K,Lamba J K,Kim R B,et al.Intestinal CYP3A4 and midazolam disposition in vivo associate with VDR polymorphisms and show seasonal variation[J].Biochem Pharmacol,2012,84(1):104-112.
5. Kliewer S A.Nuclear receptor PXR: discovery of a pharmaceutical anti-target[J].J Clin Invest,2015,125(4):1388-1389.
6. Foo W Y B,Tay H Y,Chan E C Y,et al.Meclizine,a pregnane X receptor agonist,is a direct inhibitor and mechanism-based inactivator of human cytochrome P450 3A[J].Biochem Pharmacol,2015,97(3):320-330.
7. LI JiaLi,LIU Shu,FU Qian,et al.Interactive effects of CYP3A4CYP3A5MDR1 and NR1I2 polymorphisms on tracrolimus trough concentrations in early postrenal transplant recipients[J].Pharmacogenomics,2015,16(12):1355-1365.
8. WANG XueBin,WANG Zhuo,GAO Shen,et al.Impact of CYP3A5 and ABCB1 polymorphisms on drug switching from cyclosporine to tacrolimus for individualized treatment of renal transplant recipients[J].Acad J Sec Mil Med Univ,2014,35(12):1320-1326.In Chinese with English abstract.
9. Kuehl P,Zhang J,Lin Y,et al.Sequence diversity in CYP3A promoters and characterization of the genetic basis of polymorphic CYP3A5 expression[J].Nat Genent,2001,27(4):383-391.
10. ZHANG YanQing,CHEN JinShan,LI JinYu,et al.Effects of CYP3A4/5 and PXR gene polymorphisms on plasma concentration/dosage ratio and adverse drug reactions of tacrolimus[J].Pharm Care Res,2016,16(4):251-254.In Chinese with English abstract.
11. Dring M M,Goulding C A,Trimble V I,et al.The pregnane X receptor locus is associated with susceptibility to inflammatory bowel disease[J].Gastroenterology,2006,130(2):341-348.
12. CHEN QiChen,HU ZhengWei,WANG Wei,et al.Correlation between genetic polymorphism of pregnane X receptor and ratio of tacrolimus concentration/dose in patients with renal transplantation[J].Chin J Clin Pharmacol,2016,32(17):1557-1560.In Chinese with English abstract.
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