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Background The formal recommendation for converting twice-daily tacrolimus immediate release (IR) to once-daily tacrolimus extended release (ER) is a 1:1 dose conversion. However, more recent clinical analysis has shown that this may not be true; some patients may require a higher dose. In addition, de novo dosing tacrolimus ER has revealed that African Americans require approximately 20%-30% higher doses than Caucasians to achieve similar levels. As a result, this study sought to identify the appropriate dose conversion in the African American kidney transplant population, a population at high risk of rejection. Methods This was a single-center, prospective, open-label study comparing the difference in dose-normalized trough and total daily dose necessary to reach steady-state therapeutic goal, after conversion from tacrolimus IR to tacrolimus ER, in 25 African American kidney transplant recipients. Results After conversion to tacrolimus ER, there was a significant decrease in dose-normalized trough (C0) (0.44 versus 0.59, P = 0.03). Statistically significant differences were seen in both total daily and weight-based doses, when reported as actual values (15 versus 10 mg and 0.16 versus 0.11 mg/kg, respectively), as well as when standardized to achieve a target tacrolimus C0 of 8 ng/mL (18.1 versus 13.6 mg and 0.17 versus 0.15 mg/kg, respectively). The median standardized dose conversion required was 1.3 [1.0, 1.4], for the overall population. There were no instances of biopsy-proven acute rejection, allograft loss, or study drug discontinuation. Conclusions This single-center, open-label conversion study demonstrated that there was a statistically and clinically significant decrease in dose-normalized trough after conversion from tacrolimus IR to tacrolimus ER in an African American kidney transplant population and that a 1:1 dose conversion is unlikely to meet therapeutic goals.

Background There is limited data analyzing the pharmacokinetic (PK) and pharmacodynamic (PD) properties of everolimus (EVR) between African Americans and Caucasians. The purpose of this study was to determine and compare the EVR PKs and concentration-associated efficacy and toxicity in African American and Caucasian adult kidney transplant recipients. Methods This was a retrospective PK and PD analysis of all patients who received EVR at the Medical University of South Carolina Transplant Center between 2006 and 2012. Results Forty-three patients received EVR (22 African Americans, 21 Caucasians). Baseline demographics, immunosuppression, and immunologic risk were similar between races, except for preexisting hypertension, deceased donor type, and cold ischemic time, which were higher in African American patients. PK analysis revealed that African American patients received higher initial EVR doses (2.1 ± 0.8 versus 1.6 ± 0.6 mg/d, P = 0.036), leading to higher early EVR concentrations (EVR >6 ng/mL during the first 60 days: 36% versus 10%, P = 0.037). Efficacy analysis demonstrated similar EVR effects on acute rejection rates (9% versus 10%, P = 0.961), chronic allograft changes (18% versus 14%, P = 0.729), and renal function, with both groups having improved creatinine clearance with EVR therapy (ΔeGFR: 27 versus 12 mL·min·1.73 m). Toxicity analysis demonstrated that African American patients had a trend toward higher rates of EVR discontinuation (46% versus 19%, P = 0.065) and significantly more diarrhea/gastrointestinal intolerance (73% versus 38%, P = 0.022). Conclusions These results demonstrate EVR therapy is effective at preventing rejection and improving graft function in both African American and Caucasian adult renal transplant patients. Conflicting with previous mammalian target of rapamycin PK/PD analyses in African American patients, this study cohort demonstrated higher early EVR levels in the African American patients.