The stability of amoxycillin, clarithromycin and metronidazole in gastric juice: relevance to the treatment of Helicobacter pylori infection

Abstract

Although omeprazole is an important component in anti-Helicobacter pylori therapeutic regimes using clarithromycin, amoxycillin and metronidazole, the mechanism by which it enhances antimicrobial action is unknown. One potential explanation for this effect is increased antibiotic chemical stability resulting from gastric pH changes induced by co-administration of omeprazole. The chemical stability of clarithromycin, amoxycillin and metronidazole was investigated in aqueous solutions and in human gastric juice collected before and after a 7-day course of omeprazole. Amoxycillin, clarithromycin and metronidazole were prepared in buffered aqueous solutions of pH 1.0 to 8.0 and in gastric juice of pH 2.0 and 7.0. The gastric juice samples were obtained from fasted H. pylori-negative volunteers before and after they had received a 7-day course of omeprazole. All the samples were incubated at 37 degrees C and analysed at intervals by HPLC. Amoxycillin, clarithromycin and metronidazole were stable in aqueous solutions of pH 4.0-7.0, pH 5.0-8.0 and pH 2.0-7.0, respectively. At pH 2.0, the degradation half-lives were 19.0 +/- 0.2 h, 1.3 +/- 0.05 h and 2200 +/- 1100 h, respectively. In gastric juice samples of pH 2.0, the degradation half-lives were 15.2 +/- 0.3 h, 1.0 +/- 0.04 h and > or = 800 h, respectively. The half-lives of the drugs in the gastric juice samples of pH 7.0 were all > 68 h. The co-administration of omeprazole with amoxycillin or clarithromycin is likely to increase the chemical stability of amoxycillin and clarithromycin in gastric juice. Clarithromycin degrades rapidly at normal gastric pH (1.0-2.0) but amoxycillin and metronidazole are sufficiently stable at this pH to maintain an antibacterial concentration in the stomach.

Proton pump inhibitors: from CYP2C19 pharmacogenetics to precision medicine

“…Treatment for eradication of H. pylori includes PPIs along with antimicrobial agents [68,69]. The role of PPIs is to increase the intragastric pH, allowing the bacteria to reach the growth phase and become more sensitive to antibiotics [69].…”

“…The role of PPIs is to increase the intragastric pH, allowing the bacteria to reach the growth phase and become more sensitive to antibiotics [69]. Additionally, the increased pH increases the stability of antibiotics, allowing for increased antimicrobial activity [68]. It is clear from the literature that CYP2C19 genotype impacted the outcomes of H. pylori eradication.…”

Influence of Drug Properties and Formulation on In Vitro Drug Release and Biowaiver Regulation of Oral Extended Release Dosage Forms

“…Figure 4 shows that dissolution profiles of the proportionally similar lower strength tablets (250 mg) meet the similarity factor criteria in media over the pH range of 4.5-6.8 using conventional USP test method. Data in pH 1.2 dissolution medium are unavailable because of the rapid degradation of drug B at low pH (15).…”

Formulation and In Vitro evaluation of pH sensitive oil entrapped buoyant beads of amoxicillin.

“…Drug release from the optimized formulations S 5 followed the Higuchi (R 2 = 0.943 ) and Peppas models (R 2 = 0.986, n = 0.36) , suggested a diffusion based mechanism of drug release as the diffusion exponent values were less than 0.45 [19]. Non enteric polymer ethyl cellulose was selected for coating of gel beads due to its stability in gastric pH and based on the reports on the use of ethyl cellulose for coating on floating micro particles to modify the drug release [19]. The desirable dependent response showed zero-order release pattern from EC-coated formulation in the fed state.…”

“…Various release kinetic models (zero order , Higuchi and Korshmaer-Peppas model) were applied for the elucidation of mechanism of the drug release from floating gel beads in the fed state condition [20][21][22]. Drug release from the optimized formulations S 5 followed the Higuchi (R 2 = 0.943 ) and Peppas models (R 2 = 0.986, n = 0.36) , suggested a diffusion based mechanism of drug release as the diffusion exponent values were less than 0.45 [19]. Non enteric polymer ethyl cellulose was selected for coating of gel beads due to its stability in gastric pH and based on the reports on the use of ethyl cellulose for coating on floating micro particles to modify the drug release [19].…”