Pharmacokinetics of single dose intravenous infusion of mildranate in healthy volunteers / 中国药学杂志

ABSTRACT

OBJECTIVE: To characterize the pharmacokinetics of mildranate after a single dose intravenous infusion of 250, 500 and 1000 mg in healthy subjects, and to assess the dose proportionality of mildranate over the potential therapeutic dose range of 250-1000 mg. METHODS: In a randomized three-way crossover study, twelve healthy subjects were given a single dose intravenous infusion of mildranate of 250, 500, and 1000 mg. Plasma concentrations were determined at selected time points for 24 h. The pharmacokinetic parameters were calculated by DAS software. RESULTS: The elimination half-life of mildranate after iv of 250, 500, and 1000 mg was about 5-6 h, and the peak plasma concentration (ρmax) increased linearly from (11.70±1.49) to (43.60±6.91) μg·mL-1 with increasing dosages. Moreover, the area under the plasma concentration vs time curve (AUC) increased linearly within the dose range of 250-1000 mg. The urinary excretion rate were (30.19±7.63)%, (39.64±5.02)% and (58.10±10.21)%, respectively. CONCLUSION: Mildranate exhibits a linear pharmacokinetic profile in the dose range of 250-1000 mg. Dose-dependent parameters(ρmax and AUC) increase in an approximately dose-proportional manner. There are significant differences in tmax and urinary excretion rate in the different dose groups. The differences in the pharmacokinetic parameters (tmax, ρmax, t1/2, AUC0-t, CL, Vd, MRT0-t, and urinary excretion rate) between genders are not statistically significant, but the difference in urinary excretion rate at 500 mg was statistically significant.