Pharmacokinetics and bioequivalence study of two digoxin formulations after single-dose administration in healthy Chinese male volunteers

 

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Abstract

The pharmacokinetics and relative bio-availability/bioequivalence of two formulations of digoxin (CAS 20830-75-5) were assessed in this paper. The study was conducted in 20 healthy Chinese male volunteers according to an open, randomized, single-blind, 2-way crossover study design with a wash-out phase of 14 days. Blood samples for pharmacokinetic profiling were taken up to 72 h post-dose and digoxin plasma concentrations were determined by a validated liquid chromatography-tandem mass spectrometry (LC-MS/MS) method. Based on the plasma concentration-time data of each individual during two periods, pharmacokinetic parameters, C_max, AUC_0–τ, AUC_0–∞ and t_1/2, were calculated by applying non-compartmental analysis. Pharmacokinetic data for test and reference formulations were analyzed statistically to evaluate bioequivalence of the two formulations. After oral administration, the values of C_max, T_max, t_1/2, AUC_0–τ, AUC_0–∞ for test and reference formulations were 2.61 ± 0.98 and 2.68 ± 1.09 ng/mL, 1.0 ± 0.4 and 1.0 ± 0.4 h, 27.94 ± 3.14 and 27.56 ± 3.86 h, 28.57 ± 4.99 and 28.77 ± 6.53 ng · h/mL, 33.44 ± 4.85 and 33.63 ± 7.57 ng · h/mL, respectively. Both primary target parameters, AUC_0–∞ and AUC_0–τ, were tested parametrically by analysis of variance (ANOVA). Relative bioavailabilities were 102.5 ± 19.2% for AUC_0–∞, 102.0 ± 19.3% for AUC_0–τ. Bioequivalence between test and reference formulations was demonstrated for both parameters, AUC_0–∞ and AUC_0–τ. The 90% confidence intervals of the T/R-ratios of logarithmically transformed data were in the generally accepted range of 80%–125%, which means that the test formulation is bioequivalent to the reference formulation of digoxin.

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