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<p>Kampo medicines are widely co-prescribed with Western drugs, yet package inserts typically recommend preprandial dosing. This convention can complicate co-medication schedules and may reduce adherence, while human pharmacokinetic (PK) evidence on meal-timing effects remains limited. We compared pre- versus postprandial administration of <i>maoto</i> to quantify effects on absorption rate and extent for ephedrine and pseudoephedrine. In a two-period, two-sequence crossover, eight healthy adults received ethical <i>maoto</i> extract granules (2.5&#xa0;g) 30&#xa0;min before or after a standardized meal. Plasma ephedrine and pseudoephedrine were measured by LC–MS/MS through 24&#xa0;h. PK was characterized by non-compartmental analysis (NCA) and a pre-specified one-compartment absorption model. The absorption rate constant (<i>k</i><sub><i>a</i></sub>) was the mechanistic primary endpoint; <i>AUC</i> quantified extent. Sensitivity (male-only; leave-one-out) and crossover diagnostics (sequence/period) were conducted, and model adequacy was compared by modified Akaike’s Information Criterion (AICc). Preprandial dosing yielded higher <i>C</i><sub><i>max</i></sub>, shorter <i>T</i><sub><i>max</i></sub>, and larger <i>k</i><sub><i>a</i></sub> for both analytes, indicating faster absorption. In contrast, <i>AUC</i><sub><i>0–24&#xa0;h</i></sub> and model-based <i>AUC</i><sub><i>∞</i></sub> were similar between conditions, and <i>k</i><sub><i>e</i></sub> did not differ, indicating unchanged extent and disposition. Sensitivity analyses supported these findings; no sequence or period effects were detected. AICc distributions were comparable between conditions. Meal timing primarily alters the absorption rate of ephedrine/pseudoephedrine from <i>maoto</i> without materially changing overall exposure. Preprandial dosing may be preferred when rapid onset is desired, whereas postprandial dosing remains reasonable when adherence and co-medication scheduling are prioritized.</p> Graphical abstract <p></p>

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Effect of pre- and postprandial administration of Maoto extract granules on the pharmacokinetics of ephedrine and pseudoephedrine in healthy adults

  • 期刊论文

  • 发表日期：

    2025年11月23日

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  • Toshiyuki Atsumi,
  • Takumi Nakakubo,
  • Miku Takakura,
  • Tatsunori Toida,
  • Kenji Ogata,
  • Ikuo Yamamoto,
  • Toshiaki Makino

摘要

Kampo medicines are widely co-prescribed with Western drugs, yet package inserts typically recommend preprandial dosing. This convention can complicate co-medication schedules and may reduce adherence, while human pharmacokinetic (PK) evidence on meal-timing effects remains limited. We compared pre- versus postprandial administration of maoto to quantify effects on absorption rate and extent for ephedrine and pseudoephedrine. In a two-period, two-sequence crossover, eight healthy adults received ethical maoto extract granules (2.5 g) 30 min before or after a standardized meal. Plasma ephedrine and pseudoephedrine were measured by LC–MS/MS through 24 h. PK was characterized by non-compartmental analysis (NCA) and a pre-specified one-compartment absorption model. The absorption rate constant (ka) was the mechanistic primary endpoint; AUC quantified extent. Sensitivity (male-only; leave-one-out) and crossover diagnostics (sequence/period) were conducted, and model adequacy was compared by modified Akaike’s Information Criterion (AICc). Preprandial dosing yielded higher Cmax, shorter Tmax, and larger ka for both analytes, indicating faster absorption. In contrast, AUC0–24 h and model-based AUC∞ were similar between conditions, and ke did not differ, indicating unchanged extent and disposition. Sensitivity analyses supported these findings; no sequence or period effects were detected. AICc distributions were comparable between conditions. Meal timing primarily alters the absorption rate of ephedrine/pseudoephedrine from maoto without materially changing overall exposure. Preprandial dosing may be preferred when rapid onset is desired, whereas postprandial dosing remains reasonable when adherence and co-medication scheduling are prioritized.

Graphical abstract