Piletta-Zanin Alexandre, De Mul Aurélie, Rock Nathalie, Lescuyer Pierre, Samer Caroline F, Rodieux Frédérique
Division of Clinical Pharmacology and Toxicology, Department of Anesthesiology, Pharmacology, Intensive Care and Emergency Medicine, Geneva University Hospitals, Geneva, Switzerland.
Division of Pediatric Specialties, Department of Women, Children and Adolescents, Geneva University Hospitals, Geneva, Switzerland.
Front Pharmacol. 2021 Aug 16;12:717148. doi: 10.3389/fphar.2021.717148. eCollection 2021.
Tacrolimus is a calcineurin inhibitor characterized by a narrow therapeutic index and high intra- and inter-individual pharmacokinetic variability. Therapeutic drug monitoring in whole-blood is the standard monitoring procedure. However, tacrolimus extensively binds to erythrocytes, and tacrolimus whole-blood distribution and whole-blood trough concentrations are strongly affected by hematocrit. High whole-blood tacrolimus concentrations at low hematocrit may result in high unbound plasma concentrations and increased toxicity. We present the case of a 16-year-old girl with kidney and liver transplant in whom low concentrations of tacrolimus in the context of low hematocrit led to significant increase in the dosage of tacrolimus and participate, along with a genetic polymorphism of , in nephrotoxicity.
他克莫司是一种钙调神经磷酸酶抑制剂，其治疗指数窄，个体内和个体间药代动力学变异性高。全血治疗药物监测是标准的监测程序。然而，他克莫司与红细胞广泛结合，血细胞比容对他克莫司的全血分布和全血谷浓度有强烈影响。低血细胞比容时全血他克莫司浓度高可能导致游离血浆浓度升高和毒性增加。我们报告了一名16岁肾肝移植女孩的病例，在该病例中，低血细胞比容情况下他克莫司浓度低导致他克莫司剂量显著增加，并与一种基因多态性共同参与了肾毒性。
