A multifactorial approach to tacrolimus therapeutic drug monitoring in complex liver transplantation: a case report.

This case describes a structured, multifactorial framework for interpreting tacrolimus therapeutic drug monitoring in a complex liver transplant recipient, with hypothesis-generating implications for clinical decision-making. This was a single-patient case report with serial therapeutic drug monitoring and longitudinal clinical follow-up. The clinical course of a 33-year-old male liver transplant recipient was documented in detail. During a 90-day hospitalization, the patient underwent two liver transplantations and experienced abnormal liver function, progressive anemia, and severe diarrhea, accompanied by marked fluctuations in tacrolimus trough concentrations (Ctac). Hematocrit (HCT)-corrected standardized concentrations (Cstd) were calculated using the formula Cstd = Cmeasured × (45/HCT[%]) as an interpretive aid for whole-blood Ctac during marked anemia. Across serial measurements in this single patient, tacrolimus whole-blood trough concentrations showed a positive descriptive association with HCT. Three distinct pharmacokinetic phases were identified: (1) early severe hepatic dysfunction, during which the expected CYP3A5 extensive-metabolizer phenotype appeared to be masked (peak C/D ratio: 7.70), likely attributable to compromised hepatic metabolic capacity; (2) recovery with markedly reduced HCT associated with apparently low whole-blood trough concentrations (nadir measured C: 3.2 ng/mL; corrected Cstd: 7.0 ng/mL) supporting cautious interpretation during severe anemia;and (3) inflammatory diarrhea associated with increased tacrolimus exposure (C/D ratio increased approximately 55%), possibly related to altered intestinal drug transporter and metabolic enzyme activity. Dose adjustments guided by the structured strategy successfully maintained drug exposure within the target range throughout the 90-day course without confirmed rejection episodes or severe tacrolimus-related toxicity. This case illustrates how a structured, multifactorial approach to tacrolimus therapeutic drug monitoring interpretation may assist clinical decision-making in complex post-liver-transplant settings. The proposed framework integrates pharmacological mechanisms with clinical evidence to address challenges in tacrolimus TDM interpretation. Prospective validation is required before the proposed framework can be recommended as a generalizable clinical strategy.