The influence of sampling time on sirolimus trough concentrations

Sirolimus (SRL) is a potent immunosuppressant with a long elimination half-life. Steady-state trough concentration (C0 or C24) is a reliable index of its exposure. This study was designed to understand the influence of sampling time on SRL C24. Twenty-seven stable renal transplant recipients with normal liver function who received calcineurin inhibitor (CNI)/SRL/steroid were monitored after administration of SRL tablets or solution. The SRL C24 of eighteen patients was compared with blood concentrations taken at 20 hours after dosing (C20) of nine patients. Both SRL solution and tablets produced a significantly higher dose-adjusted SRL C20 than dose-adjusted SRL C24 (mean ± SD, 3.5±1.8 vs. 2.3±1.0 ng/mL/mg for SRL solution, p＜0.01; 3.5±1.5 vs. 2.6±1.0 ng/mL/mg for SRL tablets, p=0.04) at steady state. The C20 was higher than C24 for SRL solution (mean ± SD, 5.8±2.8 vs. 4.4±2.0 ng/mL, p＜0.01), but not for tablets (mean ± SD, 5.5±3.6 vs. 4.6±2.6 ng/mL, p=0.32). All the SRL levels were within therapeutic range. Although the difference may not be clinically significant when fix-dose SRL is used, sampling time may become significant when SRL-based regimens or adjusted-dose SRL is used.