Prospective Randomized Trial Investigating the Influence of Pharmaceutical Care on the Intra-Individual Variability of Tacrolimus Concentrations Early After Kidney Transplant.

BACKGROUND: This study evaluated the influence of pharmaceutical care (PhC) in the intra-individual variability of dose-corrected whole blood tacrolimus (TAC) trough concentrations, adherence to immunosuppressive therapy and clinical outcomes. METHODS: We randomized 128 kidney transplant recipients to receive PhC consisted of predefined instructions provided by a pharmacist (PhC group, n = 64) or standard nurse staff instructions (control group, n = 64) from day 3 to day 90 after kidney transplantation. The study was powered to detect at least 50% reduction in the coefficient of variation (%CV), calculated from 6 dose-corrected whole blood TAC trough concentrations, in the PhC group. Patient adherence was evaluated using Basel Assessment of Adherence to Immunosuppressive Medication Scale (BAASIS) questionnaire. RESULTS: There was no difference in the %CV comparing PhC and control group (31.4% ± 12.3% versus 32.5% ± 16.1%, P = 0.673). There were no differences in the proportion of patients showing TAC concentrations within predefined target concentrations in each study visit. There was no difference in the proportion of nonadherent patients at day 28 (17% versus 26%, P = 0.135) and day 90 (27% versus 25%, P = 0.457) based on BAASIS questionnaire answers, respectively. There were no differences in clinical outcomes. CONCLUSIONS: Universal PhC in addition to standard nurse staff instruction was not associated with reduced intra-individual variability of dose-corrected whole blood TAC trough concentrations or improved adherence.

Concentration-controlled use of sirolimus associated with reduced exposure of cyclosporine in black recipients of primarily living renal allograft donors: 12-month results.

AIM: This study was designed to identify optimal therapeutic sirolimus (SRL) concentrations in black kidney transplant recipients on reduced cyclosporine (CsA) exposure and prednisone. METHODS: Seventy patients (64 living/six deceased) received CsA (8-10 mg/kg/d), prednisone, and 15 mg loading dose followed by 5-mg fixed doses of SRL till day 7 when they were randomized to maintain SRL trough concentrations (high-performance liquid chromatography) of 8-12 (GI = 34) or 15-20 (GII = 36) ng/mL. RESULTS: Mean CsA concentrations were 109 +/- 53 vs. 89 +/- 41 ng/mL and 75 +/- 54 vs. 60 +/- 35 ng/mL (ns) at 2 and 6 months. Accordingly, mean SRL trough concentrations were 12.4 +/- 6.1 vs. 20.0 +/- 9.5 ng/mL (p < 0.001) and 10.8 +/- 5.8 vs. 18.0 +/- 6.1 ng/mL (p < 0.001). The incidence of biopsy-proven acute rejection [13% (GI: 18% vs. GII: 8%, ns)], graft loss or death was 16% (GI: 21% vs. GII: 11%, ns]. There were no deaths and three graft losses (GI = 1; GII = 2). Creatinine clearance was higher in GI (64.5 +/- 17 vs. 54.4 +/- 14.7 mL/min, p = 0.011). The incidence of post-transplant diabetes mellitus was 13% and no CMV disease was observed. CONCLUSION: In black recipients of primarily living renal allograft donors reduced CsA exposure and SRL concentration-controlled regimens produced low incidences of acute rejection, post-transplant diabetes mellitus and CMV disease, with no significant impairment in graft function.