Co-administration of sirolimus alters tacrolimus pharmacokinetics in a dose-dependent manner in adult renal transplant recipients.
Baldan N, Rigotti P, et al.Pharmacological Research 2006; 54(3): 181-185.
Aims
To evaluate the effect of sirolimus (SIR) on tacrolimus (TAC) pharmacokinetics in adult renal transplant recipients.
Interventions
Patients were treated with TAC in two equally divided doses following transplantation, in combination with either a single morning dose of 0.5 mg SIR, versus 2.0mg. SIR was withdrawn 6 months after transplantation while the TAC daily dose remained the same in all patients.
Participants
16 stable renal allograft recipients aged ≥ 18 years
Outcomes
Primary outcomes measured were area under the curve (AUC), peak (Cmax) and trough (Cmin) TAC concentrations, oral clearance (CL/F) and time to maximum concentration (tmax). Full blood count, serum creatinine and blood pressure were also measured.
Follow-up
3 months
CET Conclusions
The authors have examined the interaction of tacrolimus (TAC) and sirolimus in adult recipients of a renal transplant. In paediatric transplant recipients co-administration of sirolimus and tacrolimus has been shown to result in a significant decrease of exposure to TAC. In adults there is conflicting information and the authors have therefore directed their attention to the effect of sirolimus on TAC pharmacokinetics in adult transplant recipients. The 16 adult patients selected who were on standard TAC plus low dose sirolimus at either 0.5mg/day or 2mg/day were examined with respect to TAC pharmacokinetics after sirolimus withdrawal. In all patients there was a significant increase in the TAC area under the curve (AUC), peak and trough levels on withdrawal of sirolimus. The authors conclude that careful monitoring of TAC levels is needed in patients receiving sirolimus and particularly after discontinuation of sirolimus.
Data analysis
Per protocol analysis
Trial registration
None