Authors
Luiz Carlos da Costa-Junior, Rita de Cássia Barbosa da Silva Tavares, Marina Izu, Simone Cunha Maradei, Maria Claudia Rodrigues Moreira, Marta Colares Nogueira, Décio Lerner, Teresa de Souza Fernandez, Paulo Caleb Júnior Lima Santos
Published in
Clinical and translational science. Volume 19. Issue 6. Pages e70637.
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.
PMID:
42286411
Bibliographic data and abstract were imported from PubMed on 13 Jun 2026.
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