Abstract: AIM: To assess the effect of wuzhicapsule (WZ) on the pharmacokinetics of midazolam, a probe drug of CYP3A4, and its metabolite 1′-hydroxymidazolam in healthy volunteers so as to study the effects of wuzhi-capsule on CYP3A4. METHODS: The study was divided into two stages.On the first stage, 12 healthy male volunteers were orally treated with 15 mg midazolam and then with 3 capsules twice daily for 7 days.On the second stage, the volunteers took another 15 mg midazolam followed by 3 capsules of wuzhi-capsule.Blood samples were taken after midazolam was given on each stage.The midazolam and 1′-hydroxy midazolam concentrations in plasma were determined by LC MS MS, and the pharmacokinetic parameters were calculated. RESULTS: The pharmacokinetic parameters of midazolam before and after coadministration with wuzhi-capsule were as follows: AUC0-24 were (578 ±227), (1186 ±320) μg·L^-1 ·h, t₁ 2 were (3.4 ±1.0), (3.6 ±1.1) h, CL (s) were(31 ±17), (14 ±6) L h, t_max were (0.8 ± 0.5), (1.6 ±1.2) h, C_max were(171 ±70), (282 ± 152) μg L,V F(C) were (149 ±98), (67 ±24) L. The pharmacokinetic parameters of 1′-hydroxy midazolam before and after coadministration with wuzhi-capsule were as follows:AUC0-24 were (141 ±699), (129 ±49) μg·L^-1·h, t₁ 2 were (5.6 ±3.3), (5.0 ±2.1) h, CL(s) were (130 ±68), (134 ±72) L h, t_max were (0.8 ±0.3), (1.6 ±1.2) h, C_max were (48 ±23), (36 ±28) μg L, V F(C) were (918 ±499), (935 ± 544) L. CONCLUSION: AUC0-24 and C_max were increased by 119.4 % and 85.6 % after midazolam administration, respectively.The CL(s) is decreased by 52.1 %.The t_max is one time longer.Wuzhi-capsule can markedly increase the blood concentration and bioavailability of midazolam.Wuzhi-capsule or some of its ingredints may be an inhibitor of CYP3A4.

Key words: wuzhi-capsule, midazolam, 1′-hydroxy midazolam, pharmacokinetics, healthy volunteers, LC MS MS, CYP3A4