Abstract

Tacrolimus is a potent but expensive first-line immunosuppressant, thus solutions to reduce tacrolimus consumption while maintain therapeutic level are in urgent need. A two-phase prospective study was conducted to assess the efficacy of an ethanolic extraction preparation of Schisandra sphenanthera (Wuzhi tablet) as a tacrolimus-sparing agent in renal transplant recipients who were high-dose tacrolimus consumers (CYP3A5*1 allele carriers, CYP3A5 expressers). A total of 12 patients were included in the Part I study. After co-administration of Wuzhi tablet, the average individual increment (%) in dose-adjusted C₀, C_max and AUC_{0–12 hour} of tacrolimus were 198.8% (95% CI 149.2, 248.3), 111.0% (95% CI 63.4, 158.6) and 126.1% (95% CI 89.4, 162.8), respectively (P < 0.01), while the average individual reduction (%) in tacrolimus daily dose was 40.9% (95% CI 25.2, 56.6) (P < 0.01). Subsequently, 32 patients were enrolled in a prospective, randomized, controlled study and randomly assigned to receive tacrolimus by CYP3A5 genotype plus Wuzhi tablet co-administration guided dosing (study group) or standard dosing (control group). Besides less tacrolimus dose requirement (P < 0.01), a more accurate tacrolimus initial dose characterized by lower incidence of out-of-range C₀ after initial dose (P < 0.01) and fewer dose changes (P < 0.01) was found in the study group. Moreover, no significant differences in acute rejection rate and serum creatinine levels were observed between two groups. Our results show that CYP3A5 genotype plus Wuzhi tablet co-administration guided tacrolimus dosing is a promising therapy for CYP3A5 expressers in the early post-transplant stage, while further study with a larger sample size is required to prove these findings.