Department of Pharmacotherapy, Meiji Pharmaceutical University, Kiyose, Tokyo, Japan.
Drugs. 2011 Oct 1;71(14):1839-64. doi: 10.2165/11593990-000000000-00000.
One may consider that drug-drug interactions (DDIs) associated with antacids is an obsolete topic because they are prescribed less frequently by medical professionals due to the advent of drugs that more effectively suppress gastric acidity (i.e. histamine H(2)-receptor antagonists [H2RAs] and proton pump inhibitors [PPIs]). Nevertheless, the use of antacids by ambulant patients may be ever increasing, because they are freely available as over-the-counter (OTC) drugs. Antacids consisting of weak basic substances coupled with polyvalent cations may alter the rate and/or the extent of absorption of concomitantly administered drugs via different mechanisms. Polyvalent cations in antacid formulations may form insoluble chelate complexes with drugs and substantially reduce their bioavailability. Clinical studies demonstrated that two classes of antibacterials (tetracyclines and fluoroquinolones) are susceptible to clinically relevant DDIs with antacids through this mechanism. Countermeasures against this type of DDI include spacing out the dosing interval - taking antacid either 4 hours before or 2 hours after administration of these antibacterials. Bisphosphonates may be susceptible to DDIs with antacids by the same mechanism, as described in the prescription information of most bisphosphonates, but no quantitative data about the DDIs are available. For drugs with solubility critically dependent on pH, neutralization of gastric fluid by antacids may alter the dissolution of these drugs and the rate and/or extent of their absorption. However, the magnitude of DDIs elicited by antacids through this mechanism is less than that produced by H2RAs or PPIs; therefore, the clinical relevance of such DDIs is often obscure. Magnesium ions contained in some antacid formulas may increase gastric emptying, thereby accelerating the rate of absorption of some drugs. However, the clinical relevance of this is unclear in most cases because the difference in plasma drug concentration observed after dosing shortly disappears. Recent reports have indicated that some of the molecular-targeting agents such as the tyrosine kinase inhibitors dasatinib and imatinib, and the thrombopoietin receptor agonist eltrombopag may be susceptible to DDIs with antacids. Finally, the recent trend of developing OTC drugs as combination formulations of an antacid and an H2RA is a concern because these drugs will increase the risk of DDIs by dual mechanisms, i.e. a gastric pH-dependent mechanism by H2RAs and a cation-mediated chelation mechanism by antacids.
人们可能认为，由于抑制胃酸的药物（即组胺 H2-受体拮抗剂[H2RAs]和质子泵抑制剂[PPIs]）的出现，抗酸剂相关的药物-药物相互作用（DDIs）已成为一个过时的话题，因为它们的使用频率已降低。尽管如此，由于抗酸剂是可在柜台上（OTC）购买的非处方药，因此，门诊患者可能会越来越多地使用它们。由弱碱性物质与多价阳离子组成的抗酸剂可能通过不同的机制改变同时给予的药物的吸收速率和/或程度。抗酸剂制剂中的多价阳离子可能与药物形成不溶性螯合物复合物，从而大大降低其生物利用度。临床研究表明，两类抗菌药物（四环素类和氟喹诺酮类）通过这种机制易与抗酸剂发生临床相关的 DDIs。针对这种类型的 DDI 的对策包括错开剂量间隔 - 在使用这些抗菌药物前 4 小时或后 2 小时服用抗酸剂。大多数双膦酸盐药物的说明书中都提到双膦酸盐可能会因与抗酸剂发生相同的机制而发生 DDIs，但目前尚无关于这些 DDI 的定量数据。对于溶解度严重依赖于 pH 值的药物，抗酸剂中和胃液可能会改变这些药物的溶解以及它们的吸收速率和/或程度。但是，通过这种机制引起的抗酸剂的 DDI 的程度小于 H2RAs 或 PPIs 引起的程度；因此，此类 DDI 的临床相关性通常不明确。一些抗酸剂配方中含有的镁离子可能会增加胃排空速度，从而加速一些药物的吸收速度。但是，在大多数情况下，这种情况的临床相关性尚不清楚，因为在短时间给药后观察到的血浆药物浓度差异很快消失。最近的报告表明，一些分子靶向药物，如酪氨酸激酶抑制剂达沙替尼和伊马替尼，以及血小板生成素受体激动剂艾曲波帕，可能会与抗酸剂发生 DDIs。最后，将 OTC 药物开发为抗酸剂和 H2RA 的组合制剂的趋势令人担忧，因为这些药物将通过两种机制增加 DDI 的风险，即 H2RA 的胃 pH 依赖性机制和抗酸剂的阳离子介导螯合机制。
