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Background and Objective <p>This study evaluated the pharmacokinetic characteristics, bioequivalence, and safety of propafenone hydrochloride tablets under fasting conditions in healthy Chinese subjects.</p> Methods <p>This was a single-center, randomized, open-label, two-formulation, single-dose study using a four-period fully replicated crossover design. A total of 36 subjects were randomized 1:1 to two sequence groups and received the test (<i>T</i>) or reference (<i>R</i>) formulation in each period. Plasma concentrations of propafenone and its active metabolite, 5-hydroxypropafenone, were quantified using a validated liquid chromatography–tandem mass spectrometry (LC–MS/MS) method. Pharmacokinetic parameters were derived by noncompartmental analysis using Phoenix WinNonlin 7.0. Bioequivalence was assessed using reference-scaled average bioequivalence (RSABE) based on the within-subject standard deviation (<i>S</i><sub>WR</sub>) of the reference product for area under the concentration–time curve from time 0 to the last time (AUC<sub>0−<i>t</i></sub>), area under the concentration–time curve from time 0 to infinity (AUC<sub>0−∞</sub>), and maximum plasma drug concentration (<i>C</i><sub>max</sub>).</p> Results <p>Overall, 35 subjects completed the study. After administration of <i>T</i> and <i>R</i>, mean (±&#xa0;standard deviation [SD]) propafenone <i>C</i><sub>max</sub>, AUC<sub>0−<i>t</i></sub>, and AUC<sub>0−∞</sub> were 52.81±70.44 versus 50.11±60.96 ng/mL, 174.98±220.13 versus 165.25±204.39 h/ng/mL, and 184.19±222.71 versus 171.31±206.53 h/ng/mL, respectively. For 5-hydroxypropafenone, <i>C</i><sub>max</sub>, AUC<sub>0−<i>t</i></sub>, and AUC<sub>0−∞</sub> were 68.95±42.09 versus 66.55±33.52 ng/mL, 234.08±150.88 versus 223.33±141.50 h/ng/mL, and 241.43±151.53 versus 230.11±142.83 h/ng/mL, respectively. RSABE analysis indicated that the geometric mean ratios (<i>T</i>/<i>R</i>) for propafenone <i>C</i><sub>max</sub>, AUC<sub>0−<i>t</i></sub>, and AUC<sub>0−∞</sub> were 101.04%, 106.27%, and 105.32%, all within the acceptance range of 80.00–125.00%.</p> Conclusions <p>Under fasting single-dose conditions, the test and reference propafenone hydrochloride tablets met bioequivalence criteria in healthy Chinese subjects.</p>

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Pharmacokinetics and Bioequivalence of Propafenone Hydrochloride Tablets under Fasting Conditions in Healthy Subjects

  • 期刊论文

  • 发表日期：

    2026年3月18日

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  • Yi Zhang,
  • Meixia Hua,
  • Lijie Du,
  • Xianmiao Yin,
  • Fangliang Gan

摘要

Background and Objective

This study evaluated the pharmacokinetic characteristics, bioequivalence, and safety of propafenone hydrochloride tablets under fasting conditions in healthy Chinese subjects.

Methods

This was a single-center, randomized, open-label, two-formulation, single-dose study using a four-period fully replicated crossover design. A total of 36 subjects were randomized 1:1 to two sequence groups and received the test (T) or reference (R) formulation in each period. Plasma concentrations of propafenone and its active metabolite, 5-hydroxypropafenone, were quantified using a validated liquid chromatography–tandem mass spectrometry (LC–MS/MS) method. Pharmacokinetic parameters were derived by noncompartmental analysis using Phoenix WinNonlin 7.0. Bioequivalence was assessed using reference-scaled average bioequivalence (RSABE) based on the within-subject standard deviation (SWR) of the reference product for area under the concentration–time curve from time 0 to the last time (AUC0−t), area under the concentration–time curve from time 0 to infinity (AUC0−∞), and maximum plasma drug concentration (Cmax).

Results

Overall, 35 subjects completed the study. After administration of T and R, mean (± standard deviation [SD]) propafenone Cmax, AUC0−t, and AUC0−∞ were 52.81±70.44 versus 50.11±60.96 ng/mL, 174.98±220.13 versus 165.25±204.39 h/ng/mL, and 184.19±222.71 versus 171.31±206.53 h/ng/mL, respectively. For 5-hydroxypropafenone, Cmax, AUC0−t, and AUC0−∞ were 68.95±42.09 versus 66.55±33.52 ng/mL, 234.08±150.88 versus 223.33±141.50 h/ng/mL, and 241.43±151.53 versus 230.11±142.83 h/ng/mL, respectively. RSABE analysis indicated that the geometric mean ratios (T/R) for propafenone Cmax, AUC0−t, and AUC0−∞ were 101.04%, 106.27%, and 105.32%, all within the acceptance range of 80.00–125.00%.

Conclusions

Under fasting single-dose conditions, the test and reference propafenone hydrochloride tablets met bioequivalence criteria in healthy Chinese subjects.