Effect of antacid on imatinib absorption
Effect of antacid on imatinib absorption
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DOI：
10.1007/s00280-008-0778-7
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发表时间：
2009-02-01
影响因子：
3
通讯作者：
Beumer, Jan H.
中科院分区：
文献类型：
--
作者：
Sparano, Brian A.;Egorin, Merrill J.;Beumer, Jan H.
伊马替尼经常引起胃部不适，导致频繁联合使用抗酸剂。胃 pH 值升高、胃排空延迟或引入 Mg2+/Al3+ 可能会改变伊马替尼的吸收，从而影响伊马替尼的治疗效果。事实上，抗酸剂与达沙替尼共同给药确实会导致达沙替尼吸收减少两倍。我们的目的是确定抗酸剂对伊马替尼药代动力学的影响。十二名健康受试者参加了一项 2 期、开放标签、随机交叉、固定序列研究。在一个周期中，每位受试者口服 400 mg 伊马替尼，而在另一周期中，在伊马替尼服用前 15 分钟，先服用相同剂量的伊马替尼，然后服用 20 mL 抗酸剂，其中含有 1.6 g Al(OH)(3) + 1.6 g Mg(OH)(2)。通过LC-MS测定伊马替尼及其活性N-去甲基代谢物CGP74588的血浆浓度，并对数据进行非房室分析。抗酸剂给药并没有显着影响血浆伊马替尼浓度与时间曲线下的面积（AUC）[单独使用31.7μg/（mL·h）与使用抗酸剂时为32.6μg/（mL·h），P = 0.37； 80%功效]。我们的结果表明，使用基于Mg2+-Al3+的抗酸剂不会显着影响伊马替尼的吸收。
Imatinib often causes gastric upset resulting in frequent co-administration of an antacid. Elevated gastric pH, delayed gastric emptying, or introduction of Mg2+/Al3+ could potentially change imatinib absorption, thereby affecting the therapeutic effectiveness of imatinib. Indeed, antacid co-administration with dasatinib does result in a twofold decrease in dasatinib absorption. We aimed to define the effect of antacid on the pharmacokinetics of imatinib.Twelve healthy subjects were enrolled in a 2-period, open-label, randomized cross-over, fixed-sequence study. In one period, each subject received 400 mg imatinib p.o., and in the other, the same dose of imatinib preceded by 20 mL antacid, containing 1.6 g Al(OH)(3) + 1.6 g Mg(OH)(2), 15 min before imatinib. Plasma concentrations of imatinib and its active N-desmethyl metabolite CGP74588 were determined by LC-MS, and data were analyzed non-compartmentally.Antacid administration did not significantly affect the area under the plasma imatinib concentration versus time curve (AUC) [31.7 mu g/(mL h) alone versus 32.6 mu g/(mL h) with antacid, P = 0.37; 80% power].Our results indicate that the use of Mg2+-Al3+-based antacid does not significantly affect imatinib absorption.