Introduction: Genetic polymorphisms in cytochrome P-450 enzymes can cause variations in tacrolimus (tac) metabolism. Ketoconazole (keto), a potent CYP450 and P-glycoprotein inhibitor, can be used concomitantly with tac to change the pharmacokinetics by slowing the metabolism and making it comparable to normal metabolizers. To date, there have been few studies evaluating long-term outcomes of rapid metabolizers on concomitant keto. The purpose of this study was to evaluate outcomes of kidney transplant recipients who are on concomitant keto and tac.

Methods: We evaluated 314 patients who received a kidney transplant between January 2013 and June 2016. Patients were divided into three groups: rapid metabolizers on concomitant tac and keto therapy, rapid metabolizers on tac only, and slow/intermediate metabolizers on tac only. Categorization of rapid and slow/intermediate metabolizers was defined through a concentration/dose ratio (C/D ratio). Rapid metabolizers were defined as those who had a C/D ratio in the first quartile of the study group at one month post-transplant (<0.89ng/ml*1/mg), slow/intermediate metabolizers were defined by C/D ratio >0.89ng/ml*1/mg.

Results: Seventy-five patients were in the keto group, 61 in the rapid metabolizer group, and 178 in the slow/intermediate group. Induction therapy was similar between the three groups where a majority of patients received alemtuzumab. At 12 months post-transplant, tac trough concentrations were similar between the groups (p=0.5448), despite higher tac dose requirements in both keto and rapid metabolizer groups compared to the slow/intermediate group (p<0.0001). There were no differences in eGFR amongst the three groups (52.5 vs 55.2 vs 52.4 ml/min, p=0.7541). Additionally, there were no differences in rejection, death-censored graft loss, death, BK viremia, or CMV infection.

Conclusion: The use of keto in rapid tac metabolizers is safe for renal transplant recipients without increasing adverse outcomes over the first 12 months. Patients requiring high doses of tac may benefit from the addition of keto.

CITATION INFORMATION: Ching J., Anders S., Janusek M., Hutchinson L., Freeman A., Patel U., Mohammed A., Bohorquez H. Long-Term Effects of Ketoconazole in Rapid Tacrolimus Metabolizers Post-Renal Transplantation Am J Transplant. 2017;17 (suppl 3).

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