Key result
Co-administration of 100 mg/kg EGCG decreased Cmax and AUC of cyclosporine A, while 3-30 mg/kg increased these parameters, and EGCG reduced the AUC of tacrolimus in rats.
Why the study?
The study investigated the effect of epigallocatechin-3-gallate on the pharmacokinetics of calcineurin inhibitors, tacrolimus and cyclosporine A, and its underlying mechanisms.
Potential interactions with calcineurin inhibitors warrant monitoring; leaves open human translation.
BACKGROUND: Epigallocatechin-3-gallate (EGCG) is the most biologically active catechin of green tea. Tacrolimus (TAC) and cyclosporine A (CsA) are immunosuppressive agents commonly used in clinical organ transplantation. The present study investigated the effect of EGCG on the pharmacokinetics of TAC and CsA in rats and its underlying mechanisms. RESEARCH DESIGN AND METHODS: Either TAC or CsA was administered to rats intravenously or orally with or without concomitant EGCG. Polymerase Chain Reaction and Western Blot were used to determine the effect of EGCG on drug-metabolizing enzymes (DMEs), drug transporters (DTs) and nuclear receptors (NRs). RESULTS: and AUC of TAC were reduced, and V/F and CL/F of TAC were enhanced after co-administration of EGCG. EGCG increased the Cmax, AUC of CsA at 3 ~ 30 mg∙kg-1 dosages, while decreased those parameters at the dosage of 100 mg∙kg-1. EGCG inhibited the mRNA and protein expressions of DMEs and DTs, such as CYP3A1, A2, UGT1A1, Mdr1 and Mrp2, but upregulated the expressions of Car, Pxr and Fxr. CONCLUSIONS: These results revealed consumption of high dose EGCG may cause a significant alteration in pharmacokinetics of TAC and distribution/elimination profiles of CsA through the regulation of DMEs, DTs and NRs.
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Huang et al. (2020) studied this question. Epigallocatechin-3-gallate (EGCG) vs. Without concomitant EGCG was evaluated on Pharmacokinetics of tacrolimus and cyclosporine A. Co-administration of 100 mg/kg EGCG decreased Cmax and AUC of cyclosporine A, while 3-30 mg/kg increased these parameters, and EGCG reduced the AUC of tacrolimus in rats.
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