Severe rise in tacrolimus levels following blood orange and grapefruit juice intake in a kidney transplant recipient: a case report.

چکیده اصلی

BACKGROUND: Tacrolimus is a cornerstone immunosuppressant in kidney transplantation with a narrow therapeutic index and high interindividual pharmacokinetic variability, largely determined by CYP3A4, CYP3A5, and P-glycoprotein activity. Grapefruit juice is a known intestinal CYP3A4 inhibitor capable of increasing tacrolimus exposure, whereas blood orange juice has not been documented to exert such effects. CASE PRESENTATION: A 33-year-old male kidney transplant recipient of Somali origin had persistently low tacrolimus trough levels, averaging about 4.5 µg/L, despite increased dosing. On postoperative day 5 (POD 5), the patient consumed approximately one liter of blood orange juice followed later the same evening by a clinically supervised 250 mL dose of grapefruit juice intended to enhance tacrolimus exposure. The following morning, his tacrolimus concentration had risen sharply sixfold to 30 µg/L, far above the increase typically associated with grapefruit juice alone. Kidney biopsy at that time showed eosinophilic infiltration, consistent with a drug-related inflammatory reaction. Tacrolimus therapy was temporarily stopped, then gradually reintroduced. His condition stabilized, and he was discharged on POD 12. CONCLUSIONS: The pronounced increase in tacrolimus exposure following sequential ingestion of blood orange and grapefruit juice suggests a potential synergistic interaction affecting tacrolimus disposition via CYP3A4, CYP3A5 and/or P-glycoprotein pathways. While causality remains unconfirmed, this case emphasizes the value of thorough dietary history in transplant care and supports further research on blood orange juice as a possible modulator of tacrolimus pharmacokinetics.

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