Effects of Diltiazem on Pharmacokinetics of Tacrolimus in relation to CYP3A5 Genotype Status in Renal Recipients: from Retrospective to Prospective.
Li JL, Wang XD, et al.The Pharmacogenomics Journal. 11(4): 300-306, 2011.
Aims
To examine the effects of diltiazem on pharmacokinetics of tacrolimus in relation to CYP3A5 genotype status in renal transplant recipients. lantation.
Interventions
Standard initial dose of tacrolimus (0.050–0.075mg/kg) without co-administration of diltiazem versus algorithm guided initial dose of tacrolimus with co-administration of diltiazem. All patients received mycophenolate mofetil and prednisolone.
Participants
32 kidney transplant recipients who were genotyped for CYP3A5*3 before transplantation
Outcomes
The primary endpoints were C0 after the initial dose, the percentage of out-of-range C0 after initial dose, the number of dose adjustments made to achieve therapeutic range and the dose requirement to reach therapeutic range. The secondary endpoints were acute rejection rate within 2 weeks after transplantation and serum creatinine on day 14 after transplantation.
Follow-up
2 weeks
CET Conclusions
Diltiazem is a calcium channel blocker which does allow a reduced dose of tacrolimus to be used in renal transplant recipients. In this study patients were randomised to an algorithm guided by the expression of the hepatic cytochrome enzyme, CYP3A5. In the presence of expression diltiazem did allow a significant reduction of the tacrolimus dosage but in those patients who were non expressers of CYP3A5 the tacrolimus sparing effect of diltiazem was not remarkable. Thus this genotype approach might allow low doses of tacrolimus to be used with diltiazem in patients expressing a CYP3A5 genotype.
Data analysis
Per protocol analysis
Trial registration
Not reported