Effects and safety evaluation of Wuzhi Capsules combined with tacrolimus for the treatment of kidney transplantation recipients

Tacrolimus (FK506), an effective and potent calcineurin inhibitor, is the cornerstone of immunosuppression after kidney transplantation. Wuzhi capsule (WZC), a prescribed ethanol extract of Nan-Wuweizi (Schisandra sphenanthera), is widely prescribed for kidney transplant recipients for the maintenance of tacrolimus concentration in clinical settings. Previous studies have demonstrated that WZC can increase the blood concentration of tacrolimus. However, it remains controversial whether to use WZC can be used to increase tacrolimus concentration in clinical practice. Our study aimed to evaluate the efficacy and safety of WZC combined with tacrolimus in the treatment of kidney transplant recipients.One hundred and ninety four Chinese kidney transplant recipients were included in this retrospective study. The recipients were divided into two groups (non-WZC group and WZC group). We investigated the effects of WZC on tacrolimus in terms of tacrolimus metabolism, laboratory tests, pharmacogenomics, renal function and adverse reactions.The concentration/dose (C0 /D) of tacrolimus was significantly higher in the WZC group than the non-WZC group. The laboratory findings of blood routine tests, liver and kidney function were not significantly different between the two groups. The CYP3A5 genotype showed clearly associated with tacrolimus C0 /D, whereas no significant difference was observed in patients with CYP3A4*1B, CYP3A4*22, ABCB1, ABCC2, POR*28 or PXR alleles. The improvement of C0 /D by administration of WZC was significant in CYP3A5 expressers compared to non-expressers. Furthermore, the WZC group had a remarkably higher proportion of subjects who reached the target tacrolimus concentration than the non-WZC group. No significant differences in renal function and adverse reactions were observed between the groups.Wuzhi capsule can increase tacrolimus concentration without negative effects on renal function and adverse reactions, especially in CYP3A5 expressers. Efficient and economical synergistic effects can be achieved by the combined administration of WZC in kidney transplant recipients.