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ABSTRACT Tacrolimus pharmacokinetics shows wide interindividual variability after allogeneic hematopoietic cell transplantation (HCT), potentially influencing both effectiveness and toxicity. The concentration‐to‐dose (C/D) ratio has been proposed as a simple surrogate marker of tacrolimus metabolism, enabling patient stratification into fast or slow metabolizers. In this retrospective single‐center study, we evaluated the clinical applicability of the C/D ratio in 71 HCT recipients treated between 2014 and 2023. Fast metabolizers (< 420 ng/mL·1/mg/kg) required higher tacrolimus doses and exhibited lower trough concentrations compared with slow metabolizers (≥ 420). Slow metabolizers had a higher risk of moderate‐to‐severe acute kidney injury (AKI) within 21 days after starting tacrolimus (HR 3.72; 95% CI 1.19–11.61; p = 0.024). In contrast, fast metabolizers showed a trend toward increased incidence of acute graft‐versus‐host disease (aGVHD) (HR 1.91; 95% CI 0.93–3.92) and an almost universal need for dose escalation (96.8%). Tacrolimus metabolism exerts opposing effects on renal safety and immunosuppressive effectiveness, with faster clearance predisposing to immune activation and slower clearance to early AKI. The C/D ratio provides an early pharmacokinetic snapshot capable of anticipating individual exposure patterns and may serve as a practical tool to guide proactive dosing and optimize the balance between effectiveness and safety in HCT recipients.
Costa et al. (Mon,) studied this question.