Limited utility of cyclosporine C2 monitoring in heart transplant recipients receiving ketoconazole.

The aim of the study was to compare 2 hours postdose concentration (C2) of CyA in stable patients receiving ketoconazole concomitantly late after heart transplantation (OHT) with patients not receiving ketoconazole. Routine C2 and C1 (1 hour postdose concentration) of CyA monitoring (FPIA, AxSYM, Abbott) along with C0 (trough level) were performed in 64 elective patients. The KETO group consisted of 29 patients receiving 200 mg of ketoconazole daily along with CyA; the remaining 35 patients were included into the control group. Patient characteristics (KETO vs control group) were as follows: age, 49 +/- 11 versus 48 +/- 12 years; percentage of male patients, 93 versus 80; follow-up post-OHT, 4.3 +/- 2 versus 5.3 +/- 2 years. Target C0 of CyA was 175 to 225 ng/mL; CyA doses remained stable for at least 1 month. We compared maintenance doses of CyA, C0, C1, C2 of CyA, number of biopsy-proven acute cellular rejection (AR) during the one year and after the first year post-OHT, and creatinine in both groups. Statistical significance was assessed using Mann-Whitney U test. Results were as follows (KETO versus control group): CyA dose, 53 +/- 30 versus 216 +/- 69 mg, P <.000001; C0, 181 +/- 77 versus 160 +/- 53 ng/mL, NS; C1, 406 +/- 78 versus 803 +/- 317 ng/mL, P =.000001); C2, 397 +/- 174 versus 689 +/- 284 ng/mL, P =.000001, AR during the first year after OHT, 2.8 +/- 1.9 versus 2.3 +/- 1.6, NS; AR beyond first year after OHT, 0.2 +/- 0.5 versus 0.7 +/- 0.9, P =.03); creatinine, 181 +/- 50 versus 160 +/- 114 micromol/L NS. In conclusion; C2 monitoring in stable heart transplant recipients receiving cyclosporine and ketoconazole concomitantly late after procedure does not seem to be sufficient to estimate the immunosuppressive effect of this combination.

RCT Entities:   Population Interventions Outcomes