Drug Metab Dispos 2017 11 1;45(11):1114-1119. Epub 2017 Sep 1.
Institute of Clinical Pharmacology, School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou, China (J.L., X.Q., H.B., Y.Z., X.W., M.H.); Kidney Transplant Department, Transplant Center, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, China (S.C., Q.F., L.L., C.W.); Guangdong Food and Drug Vocational College, Guangzhou, China (X.Q.); and School of Pharmaceutical Sciences, Guangzhou Medical University, Guangzhou, China (Y.Z.)
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 (Wuzhi tablet) as a tacrolimus-sparing agent in renal transplant recipients who were high-dose tacrolimus consumers ( 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 C, C and AUC 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 ( < 0.01), while the average individual reduction (%) in tacrolimus daily dose was 40.9% (95% CI 25.2, 56.6) ( < 0.01). Subsequently, 32 patients were enrolled in a prospective, randomized, controlled study and randomly assigned to receive tacrolimus by genotype plus Wuzhi tablet co-administration guided dosing (study group) or standard dosing (control group). Besides less tacrolimus dose requirement ( < 0.01), a more accurate tacrolimus initial dose characterized by lower incidence of out-of-range C after initial dose ( < 0.01) and fewer dose changes ( < 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 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.