Effect of ingested fluid volume and solution osmolality on intestinal drug absorption: Impact on drug interaction with beverages
Effect of ingested fluid volume and solution osmolality on intestinal drug absorption: Impact on drug interaction with beverages
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DOI：
10.1016/j.ejps.2022.106136
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发表时间：
2022-02-15
影响因子：
4.6
通讯作者：
Shirasaka, Yoshiyuki
中科院分区：
文献类型：
--
作者：
Funai, Yuta;Takemura, Miyuki;Shirasaka, Yoshiyuki
最近的研究表明，渗透压依赖性液体运动是导致临床观察到的苹果汁（AJ）-阿替洛尔相互作用的重要因素。在这里，我们研究了渗透压依赖性液体运动是否也可以解释AJ-阿替洛尔相互作用的AJ体积依赖性。在Wistar大鼠中，给予不同体积的纯化水（0.5和1.0 mL）后，管腔液体体积逐渐减少至相似的稳态水平，而给予不同体积的AJ（0.5和1.0 mL）后，管腔液体体积增加并达到不同的表观稳态水平。假设渗透压依赖性液体分泌可解释表观稳态的体积依赖性。事实上，FD 4（一种非渗透性化合物）在AJ中给药后的管腔浓度根据摄入量而衰减，而在纯化水中给药后的管腔浓度与摄入的液体体积无关。大鼠体内药代动力学研究表明，AJ和高渗溶液（调整至AJ的渗透压摩尔浓度）与阿替洛尔联合给药可显著降低阿替洛尔的AUC和C-max，且呈体积依赖性。这些结果表明，渗透压依赖性变化的管腔液体体积可能间接影响药物的吸收特性，并可以解释所观察到的体积依赖性的饮料-药物相互作用。
It was recently shown that osmolality-dependent fluid movement is a significant factor causing the clinically observed apple juice (AJ)-atenolol interaction. Here we examined whether osmolality-dependent fluid movement may also explain the AJ volume dependence of the AJ-atenolol interaction. In Wistar rats, the luminal fluid volume after administration of different volumes of purified water (0.5 and 1.0 mL) gradually reduced to a similar steady-state level, while that after administration of different volumes of AJ (0.5 and 1.0 mL) increased and attained different apparent steady-state levels. It was hypothesized that osmolality-dependent fluid secretion would account for the volume dependence of the apparent steady-state. Indeed, the luminal concentration of FD 4, a non-permeable compound, after administration in AJ was attenuated depending upon the ingested volume, whereas that after administration in purified water was independent of the ingested fluid volume. An in vivo pharmacokinetic study in rats showed that co-administration of AJ and hyperosmotic solution (adjusted to the osmolality of AJ) with atenolol volume-dependently reduced the AUC and C-max of atenolol significantly. These results show that osmolality-dependent variations in luminal fluid volume may indirectly influence the absorption characteristics of drugs, and can account for the observed volume dependence of beverage-drug interactions.