Tacrolimus, Cytochrome P450, Interactions with Food Variables in Organ Transplant Recipients; A Current and Comprehensive Review

Abstract

The well-established calcineurin inhibitor, tacrolimus, as an immunosuppressive agent, is widely prescribed after organ transplantation. Cytochrome P450 (CYP 450) isoforms are responsible for the metabolism of many features associated with food parameters like phytochemicals, juices, and fruits. This review article summarizes the findings of previous studies to help predict the efficacy or side effects of tacrolimus in the presence of food variables. From the commencement of databases associated with the topic of interest to 26 October 2024, all relevant articles were searched through PubMed, Scopus, and Web of Science. The suggested therapeutic range for tacrolimus trough concentration (C(0) ) was reported as 5-15 ng/ml blood. Tacrolimus interaction with food variables could significantly change C(0) after organ transplantation. For example, grapefruit juice could increase tacrolimus C(0) due to CYP enzyme inhibition. Toxicity such as nephrotoxicity could result from turmeric and other herbal or food products. By inhibiting tacrolimus-metabolizing enzymes and transporters, a high intake of vegetables could increase the risk of adverse effects. Secondary metabolites of vegetables could lead to toxicity in patients with tacrolimus. Furthermore, grapefruit juice, citrus fruits, turmeric, and pomegranate juice could change clinical pharmacokinetics parameters such as T(max), C(max), AUC, and C(0) of tacrolimus after organ transplantation. Bioavailability of tacrolimus might be decreased by induction of the CYP450 system and P-gp efflux pump due to cranberry, rooibos tea, and boldo. Increased inhibitory effect on CYP450 system and/or P-gp efflux pump by grapefruit juice, schisandra, berberine, turmeric, pomegranate juice, pomelo, and ginger could increase bioavailability of tacrolimus. A vigilant immunosuppressive strategy accompanied by scheduled therapeutic drug monitoring is recommended before and after transplant surgery.