Drug Absorption Interactions Between Oral Targeted Anticancer Agents and PPIs: Is pH-Dependent Solubility the Achilles Heel of Targeted Therapy?
Drug Absorption Interactions Between Oral Targeted Anticancer Agents and PPIs: Is pH-Dependent Solubility the Achilles Heel of Targeted Therapy?
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DOI：
10.1038/clpt.2012.73
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发表时间：
2012-08-01
影响因子：
6.7
通讯作者：
Ware, J. A.
中科院分区：
文献类型：
--
作者：
Budha, N. R.;Frymoyer, A.;Ware, J. A.
大多数新型口服的口服，分子靶向的抗癌疗法都是表现出pH依赖性溶解度的弱碱基，而降低酸性剂抑制胃酸性可能会损害其吸收。此外，大多数癌症患者经常服用减少酸性剂来减轻胃食管反流疾病的症状，从而增加了可能减少抗癌药物暴露的常见但不足的药物相互作用（DDI）的可能性，从而导致抗癌药物的暴露并在随后的治疗失败中导致。本文回顾了可用的临床文献，该文献描述了15种口头施用的小分子靶向抗癌疗法和降低酸性药物之间相互作用的程度。当前可用的临床数据表明，该DDI的幅度最大，对于其体外溶解度在pH范围1-4上变化的化合物最大。该范围代表正常的生理胃酸性（类似于1）和胃酸性，而在酸还原剂上（pH类似于4）。
A majority of the novel orally administered, molecularly targeted anticancer therapies are weak bases that exhibit pH-dependent solubility, and suppression of gastric acidity with acid-reducing agents could impair their absorption. In addition, a majority of cancer patients frequently take acid-reducing agents to alleviate symptoms of gastroesophageal reflux disease, thereby raising the potential for a common but underappreciated drug-drug interaction (DDI) that could decrease the exposure of anticancer medication and result in subsequent failure of therapy. This article is a review of the available clinical literature describing the extent of the interaction between 15 orally administered, small-molecule targeted anticancer therapies and acid-reducing agents. The currently available clinical data suggest that the magnitude of this DDI is largest for compounds whose in vitro solubility varies over the pH range 1-4. This range represents the normal physiological gastric acidity (pH similar to 1) and gastric acidity while on an acid-reducing agent (pH similar to 4).