Prograf produces more benefits for CYP3A5 low expression patients in early stage after kidney transplantation.
OBJECTIVE
This study is to analyze concentration changes of the prolonged-release and shorter-acting formulation of tacrolimus in patients with different CYP3A5 genotypes after kidney transplantation.


METHODS
A single-factor retrospective analysis was performed in patients underwent allogeneic kidney transplantation with postoperative administration of Advagraf or Prograf in our hospital from May 2013 to June 2014. The CYP3A5 genotypes were determined, and tacrolimus trough concentrations in whole blood were measured within 28days after transplantation. The rates of acute rejection rate, chronic rejection and infection were recorded and compared after one year follow-up after surgery.


RESULTS
The study included 106 patients administered Advagraf (45 cases) or Prograf (61 cases). The low expression genotype of CYP3A5 was detected in 40 (37.7%) patients. A higher dose of Advagraf was required to increase the tacrolimus trough concentrations within 21days after transplantation. Moreover, a higher dose for Advagraf than Prograf was required to increase the tacrolimus trough concentrations in low expression patients. In the low expression patients, Prograf more frequently achieved the target tacrolimus trough concentrations within seven days after transplantation (five days: 7.14% vs. 84%, P=0.001; seven days: 33.33% vs. 77.78%, P=0.001). The patient and kidney graft survival rates one year after transplantation both were 100%. The estimated glomerular filtration rate showed no significant difference between different CYP3A5 phenotypes or formulations of tacrolimus (P>0.05). However, the incidence of infections was higher in the Advagraf group in low expression patients (P<0.05).


CONCLUSIONS
Tacrolimus of different formulations had different impact on patients with different CYP3A5 genotypes after kidney transplantation.
Department of Urology, Beijing ChaoYang Hospital, Capital Medical University, Beijing 100020, PR China.
Bohan
B
Fan
Department of Pharmacy, Beijing ChaoYang Hospital, Capital Medical University, Beijing 100020, PR China.
Kui
K
Qiu
Department of Urology, Beijing ChaoYang Hospital, Capital Medical University, Beijing 100020, PR China.
Yihang
Y
Jiang
Department of Urology, Beijing ChaoYang Hospital, Capital Medical University, Beijing 100020, PR China.
Xiaopeng
X
Hu
Department of Urology, Beijing ChaoYang Hospital, Capital Medical University, Beijing 100020, PR China.
Hang
H
Yin
Department of Urology, Beijing ChaoYang Hospital, Capital Medical University, Beijing 100020, PR China.
Wei
W
Wang
Department of Urology, Beijing ChaoYang Hospital, Capital Medical University, Beijing 100020, PR China.
Liang
L
Ren
Department of Urology, Beijing ChaoYang Hospital, Capital Medical University, Beijing 100020, PR China.
Hang
H
Liu
Department of Urology, Beijing ChaoYang Hospital, Capital Medical University, Beijing 100020, PR China.
Wei
W
Wang
Department of Urology, Beijing ChaoYang Hospital, Capital Medical University, Beijing 100020, PR China. Electronic address: syfanbh@sina.com.
Xiaodong
X
Zhang
D000328:Adult; D051544:Cytochrome P-450 CYP3A / Q000096:biosynthesis / Q000235:genetics*; D004339:Drug Compounding; D005260:Female; D005838:Genotype; D005919:Glomerular Filtration Rate; D006084:Graft Rejection / Q000517:prevention & control; D006085:Graft Survival / Q000187:drug effects; D006801:Humans; D007166:Immunosuppressive Agents / Q000009:adverse effects / Q000627:therapeutic use*; D016030:Kidney Transplantation / Q000379:methods*; D008297:Male; D008875:Middle Aged; D012189:Retrospective Studies; D013530:Surgical Wound Infection / Q000453:epidemiology / Q000276:immunology; D016559:Tacrolimus / Q000009:adverse effects / Q000627:therapeutic use*; D055815:Young Adult
D007166:Immunosuppressive Agents; C510164:CYP3A5 protein, human; D051544:Cytochrome P-450 CYP3A; D016559:Tacrolimus
Advagraf; CYP3A5 genotype; Coefficient of variation; Kidney transplantation; Prograf; Tacrolimus