1.Influence of CYP3A5*3 Genetic Polymorphism on Blood Concentration of Tacrolimus and Renal Function in Renal Transplant Recipients during the Stable Period
Zewu WEI ; Xuebin WANG ; Wenwen ZHANG ; Yunyun YANG ; Lihong GAO ; Duoling MA ; Chengwu XIAO ; Zhuo WANG ; Shen GAO
China Pharmacy 2018;29(2):183-187
OBJECTIVE:To investigate the influence of CYP3A5*3 (rs776746) genetic polymorphism on blood concentration of tacmlimus (TAC) and renal function in renal transplant recipients during the stable period.METHODS:A total of 98 renal transplant recipients during the stable period receiving TAC-based triple anti-rejection scheme (TAC + sodium mycophenol +predrnisone acetate) after surgery and regular follow-up were selected from our hospital during Jan.1995-Dec.2014.The follow-up information during Jan.-Dec.2016 was also collected.Trough concentration of TAC in renal transplant recipients was determined by chemiluminescence microparticle immuno assay.Standard blood concentration (C/D) was calculated after corrected with body weight and daily dose.Scr level was detected with dry chemistry method.CYP3A5*3 genotype was detected by PCR-RFLP and direct sequencing.The relationship of CYP3A5*3 genetic polymorphism with TAC C/D value and Scr level was determined by Kruskal Wallis H or Mann-Whitney U assay.RESULTS:Among 98 renal transplant recipients,there were 9 cases of CYP3A5*3 *1/*1(AA) genotype,37 cases of *1/*3 (AG) genotype and 52 cases of *3/*3 (GG)genotype.The gene frequencies were 9.18%,37.76%,53.06%,which were all in line with Hardy-Weinberg equilibrium (P>0.05).There was no statistical significance in trough concentration of TAC among different genotypes (P>0.05).There was statistical significance in TAC dose and C/D value among different genotypes (P>0.05).TAC dose of CYP3A5*3 *3/*3 genotype recipients was significantly lower than those of *1/*3 and *1/*1 genotype recipients;that of *1/*3 genotype recipients was significantly lower than that of *1/*1 genotype recipients.C/D value of *3/*3 genotype recipients was significantly higher than those of *1/*3 and *1/*1 genotype recipients;that of *1/*3 genotype recipients was significantly higher than that of *1/*1 genotype recipients,with statistical significance (P<0.05).There was no statistical significance in Scr levels among different genotypes (P>0.05).CONCLUSIONS:CYP3A5*3 genetic polymorphism significantly influences blood concentration of TAC in renal transplant recipients during the stable period,and *3 allele carriers have higher C/D values and need smaller TAC daily dose.CYP3AS*3 genetic polymorphism may be not associated with Scr level.
2.A retrospective analysis of the efficacy and adverse reactions for the renal trans-plant patients conversed from cyclosporine A to tacrolimus
Zewu WEI ; Wenwen ZHANG ; Duoling MA ; Juan BI ; Jiexiu CHEN ; Yunyun YANG
Journal of Pharmaceutical Practice 2018;36(1):75-79
Objective To study the efficacy and adverse reactions for renal transplant patients conversed from cyclospo-rine A to tacrolimus .Methods The follow-up data of renal transplant patients conversed from cyclosporine A to tacrolimus were collected .The clinical therapeutic outcomes including drug induced diseases (DIDs) and acute rejection (AR) induced by cyclosporine A were analyzed during the first year after conversion with SPSS 17 .0 software .Results The levels of Scr and BUN were significantly decreased during the first year after conversion for renal transplant patients with CScr and AR (P<0.05 or P<0 .01) .The levels of direct bilirubin (DB) and total bilirubin (TB) were also significantly lowed (P<0.05 or P<0 .01) during the first year for drug-induced liver injury (DILI) patients .The average level of ALT was significantly decreased in 12 months after conversion (P<0.05) .The complications of gingival overgrowth (GO) stopped with the medication replace-ment .However ,the fasting blood glucose (FBG) level increased significantly in 12 months after conversion (P<0.05) .Con-clusion For renal transplant patients suffered from AR or the serious DIDs induced by cyclosporine A ,conversion from cyclos-porine A to tacrolimus could be considered .However ,it should be aware of the high blood glucose or the new diabetes caused by tacrolimus .