Background: The aim of the study was to assess pharmacokinetics of twice a day versus once-daily tacrolimus in kidney transplant recipients.
Material/Methods: The study included 44 stable kidney transplant recipients who were transplanted between 2001 and 2008. Among them were 21women and 23 men aged from 17 to 68 y. (45±13). Immunosuppressive therapy consisted of tacrolimus and mycophenolate mofetil in 28 cases, mycophenolate sodium in 6 cases, azathioprine in 3 cases and prednisone in 43 cases. Kidney allograft function was stable before conversion and eGFR were 50±16 ml/min. Patients were converted from twice a day tacrolimus to the same milligram-for-milligram daily dose of once-daily tacrolimus taken in the morning. Blood samples were collected just before and after 14 days of conversion. Tacrolimus trough levels in whole blood were assessed by the Abbott IMx system.
Results: The mean tacrolimus dose was 4.4±1.7 mg/day. The mean trough level before conversion was 6.9±1.9 ng/ml. After 14 days of conversion the mean through level was lower: 5.6±1.9 ng/ml (the decrease of 19%). After conversion 11 (25%) patients presented stable trough levels. Changes in tacrolimus concentration were observed in 33 (75%) patients. In 28 patients (64%) a decrease of trough level and in 5 patients (11%) an increase was noticed. The dose adjustment after conversion due to potential subtherapeutic levels was required in total of 16 (36%) patients. All the recipients presented stable allograft function during the observation period (>2 months) after conversion. Conclusions: The results provide evidence to support a safety 1:1 conversion from twice a day versus once-daily formulation of tacrolimus. Trough levels must be monitored carefully at the early post-conversion period since a dose adjustment may be required.

Keywords: Pharmacokinetics, immunosuppressive therapy, azathioprine