Acid intolerance of macrolides: clinical significance and ways of correction

Purpose of the study. To draw the attention of gastroenterologists to the high intensity of intragastric acid production as a factor that can reduce the clinical effectiveness of macrolide antibiotics prescribed both for the eradication of H. pylori and for other indications. Materials and methods. A review of published data was performed with general information on macrolides, information on their comparative acid resistance, methods of protecting active substances from the effects of the acidic environment of the stomach and the reasons for the failure of this protection. Results of the study. Among the widely used macrolides, roxithromycin is the most acid-resistant. Erythromycin, rarely prescribed as a prokinetic, is produced in dosage forms with enteric coatings. Clarithromycin, which has average acid resistance, is prescribed with PPIs for the eradication of H. pylori. It is known that the resistance of H. pylori to clarithromycin, caused mainly by the presence of nucleotide substitutions in the binding region of macrolide antibiotics in the 23S molecule, has reached 28.9% in some regions of the world. Some researchers have noted that the intensity of the antisecretory effect of PPIs depends on the individual characteristics of the patient’s metabolism using CYP2C19. According to our data, clarithromycin may be partially destroyed in an acidic environment if it is used together with PPIs in dosage forms with poor-quality enteric coatings that can be destroyed under conditions of fulfilled Bell’s rule or under the influence of pathological duodenogastric reflux. This factor has been demonstrated by experimental data. Conclusion. Current clinical practice does not take into account the relationship between the chemical and pharmaceutical properties of macrolides and the drugs used together with them, with their clinical efficacy, namely: When prescribing macrolides in oral dosage forms, their comparative acid instability and the likely presence of conditions in patients associated with high intensity of intragastric acid production should be taken into account; The ineffectiveness of H. pylori eradication when using triple therapy with clarithromycin may be associated not only with the resistance of the pathogen to the macrolide, but also with instability in the acidic environment of enteric-coated forms of simultaneously prescribed proton pump inhibitors.

macrolides, erythromycin, clarithromycin, azithromycin, acid intolerance, enteric coatings, enteric polymers, Helicobacter pylori eradication, resistance, pseudoresistance

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