Evaluation of everolimus pharmacokinetic monitoring based on trough concentration and area under the blood concentration time curve in kidney transplantation.

backgroundEverolimus (EVR) is widely used in kidney transplantation; however, the optimal sampling time point for therapeutic drug monitoring and the relationship between EVR exposure and adverse events under tacrolimus-based regimens remain unclear.

methodsWe retrospectively analyzed EVR pharmacokinetics in kidney transplant recipients receiving tacrolimus-based immunosuppressive therapy. EVR whole-blood concentrations at multiple post-dose time points were compared with the area under the concentration–time curve from 0 to 4 hours (AUC₀–₄). Associations between EVR exposure and adverse events, including proteinuria and de novo hyperlipidemia (HL), were explored using statistical models accounting for repeated pharmacokinetic measurements.

resultsEVR concentration at 2 hours post-dose (C2) showed the strongest correlation with AUC₀–₄ and was superior to trough concentration (C0) as a surrogate marker of short-term systemic exposure. Short-term EVR systemic exposure (AUC₀–₄) was not independently associated with de novo HL, whereas longer treatment duration was strongly associated with lipid abnormalities. No significant association was observed between EVR exposure and proteinuria.

conclusionsC2 represents a practical surrogate marker for short-term EVR exposure in kidney transplant recipients receiving tacrolimus-based therapy. While EVR exposure itself was not independently associated with de novo HL, treatment duration appears to be an important factor, underscoring the need to consider long-term metabolic effects during EVR therapy.