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Hirotoshi Echizen – One of the best experts on this subject based on the ideXlab platform.

  • Clinically Significant Drug Interactions with Antacids
    Drugs, 2011
    Co-Authors: Ryuichi Ogawa, Hirotoshi Echizen

    Abstract:

    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 antibacterial s (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.

  • clinically significant drug interactions with Antacids an update
    Drugs, 2011
    Co-Authors: Ryuichi Ogawa, Hirotoshi Echizen

    Abstract:

    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 H2-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.

Daniel C. Sadowski – One of the best experts on this subject based on the ideXlab platform.

  • Drug Interactions with Antacids
    Drug Safety, 1994
    Co-Authors: Daniel C. Sadowski

    Abstract:

    Concomitant use of antacid preparations with other medications is common. The potential for antacid-drug interactions is dependent upon the chemistry and physical properties of the antacid preparation. The intragastric release of free aluminum and magnesium ions has potent effects on gastrointestinal function and on drug pharmacokinetics. Antacid-drug interactions may occur secondary to changes in gastrointestinal motility or alterations in gastric and urinary pH. Direct adsorption also results in decreased drug bioavailability. Human drug interaction studies are usually performed with healthy volunteers; extrapolation of these results to clinical situations may not always be valid. However, the current literature would suggest that significant interactions with Antacids do occur with certain members of the quinolone, nonsteroidal anti-inflammatory drug (NSAID) and cephalosporin classes of drugs. Notable interactions also occur with tetracycline, quinidine, ketoconazole and oral glucocorticoids. These interactions are particularly relevant in the patient with sepsis, cardiac disease or inflammatory syndromes.

  • drug interactions with Antacids mechanisms and clinical significance
    Drug Safety, 1994
    Co-Authors: Daniel C. Sadowski

    Abstract:

    Concomitant use of antacid preparations with other medications is common. The potential for antacid-drug interactions is dependent upon the chemistry and physical properties of the antacid preparation. The intragastric release of free aluminum and magnesium ions has potent effects on gastrointestinal function and on drug pharmacokinetics. Antacid-drug interactions may occur secondary to changes in gastrointestinal motility or alterations in gastric and urinary pH. Direct adsorption also results in decreased drug bioavailability. Human drug interaction studies are usually performed with healthy volunteers; extrapolation of these results to clinical situations may not always be valid. However, the current literature would suggest that significant interactions with Antacids do occur with certain members of the quinolone, nonsteroidal anti-inflammatory drug (NSAID) and cephalosporin classes of drugs. Notable interactions also occur with tetracycline, quinidine, ketoconazole and oral glucocorticoids. These interactions are particularly relevant in the patient with sepsis, cardiac disease or inflammatory syndromes.

J. Vatier – One of the best experts on this subject based on the ideXlab platform.

  • An artificial stomach-duodenum model for the in-vitro evaluation of Antacids.
    Alimentary Pharmacology & Therapeutics, 2007
    Co-Authors: J. Vatier, E. Malikova-sekera, M. Mignon

    Abstract:

    To improve the dynamic in-vitro evaluation of the effects of Antacids, we have developed the ‘artificial stomach’ model by adding a ‘duodenal reservoir’ to receive the gastric emptying flux and simulated bicarbonate secretion, thus constituting an ‘artificial stomach-duodenum’ model. With this model we measured antacid-induced resistance to gastric acidification, and simultaneously evaluated the effect of antacid activity on the duodenal milieu. The model also permitted evaluation of the antacid effects of proteins (as natural Antacids), and of drugs containing aluminium phosphate, alone or combined with magnesium oxide, or aluminium and magnesium hydroxides. At the gastric site, these drugs, as well as the proteins (that is, meat extract), induced a strong resistance to acidification due to the gastric emptying flux and to antacid composition. At the duodenal site, the decrease of the acid load penetrating into the duodenum varied, depending on the efficacy of gastric antacid activity. Duodenal pH was related to the equilibrium between bicarbonate secretion and the emptying of acid load. Proteins and aluminium phosphate induced the same duodenal pH as in the control tests without Antacids, but magnesium-containing Antacids increased it, thus decreasing bicarbonate consumption. The antacid mechanisms within the stomach, and the fate of Antacids in the duodenal milieu, might explain the variation in duodenal pH in response to antacid administration.

  • interactions of cimetidine and ranitidine with aluminum containing Antacids and a clay containing gastric protective drug in an artificial stomach duodenum model
    Journal of Pharmaceutical Sciences, 1994
    Co-Authors: J. Vatier, A Harman, N Castela, M T Droylefaix, R Farinotti

    Abstract:

    Interactions of cimetidine and ranitidine with aluminum-containing Antacids and clay-containing gastric-protective drugs were analyzed in vitro by using an artificial stomach-duodenum model. The model reproduced near-physiologic conditions, taking into account gastric and duodenal flux variations and interactions between gastric mucosa and drugs added to the gastric content. Clay bound cimetidine in acid medium, but the drug was released when the pH increased, resulting in cimetidine amounts in the duodenal site close to those in controls. In contrast, clay bound ranitidine in acid medium and did not release it in the duodenal site. Aluminum-containing Antacids did not significantly modify the amount of cimetidine or ranitidine available for absorption. Several factors play a role in the interactions of cimetidine and ranitidine with aluminum-containing Antacids and clay-containing gastric-protective drugs: the structure of the antisecretory drugs, gastroduodenal pH, interactions of the antacid and clay with the gastric mucosa, and release of aluminum that could adsorb the drugs or prevent their adsorption by the mucosa. These phenomena are intricate and difficult to analyze without using a physicochemical approach.

  • New approach for the in vitro evaluation of Antacids.
    Drug Research, 1990
    Co-Authors: J. Vatier, Vallot T, Mignon M

    Abstract:

    Evidence is given that the in vitro evaluation of Antacids has been incomplete, not regarding physiopathological conditions. As a consequence arbitrary antacid potency classifications were introduced and in clinical practice high dosages of antacid drugs were prescribed. The main reason is that the in vitro evaluation procedures used did not take into account the actual conditions of gastric acid secretion. The proposed methods allow to assess antacid activity under conditions similar to those during gastric secretion. “Pharmacologically”, the capacity of binding H+ ions in acid milieu can be quantified and the antacid mechanism can be characterized. “Therapeutical efficacy” might be analysed under acid conditions taking into account gastric intraluminal flux variations by using the “artificial stomach” model. This procedure also allows to evaluate the influence of gastric protein content on antacid activity and to simulate the actual gastric conditions by using human gastric juice as gastric content and as simulated “secretion”. The antacid-induced resistance to acidification largely corresponds to the therapeutical antacid activity. Data obtained with aluminum containing Antacids are presented.