Effect of pH variation on the susceptibility ofHelicobacter pylori to three macrolide antimicrobial agents and temafloxacin

Malanoski, Gregory J.; Eliopoulos, George M.; Ferraro, Mary Jane; Moellering, Robert C.

doi:10.1007/bf01967591

Cited by 54 publications

(16 citation statements)

References 12 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Evidence suggests that eradication of H. pylori is associated with faster healing and a significant decrease in peptic ulcer recurrence (18). Previous studies have demonstrated the susceptibility of H. pylori to various antibiotics or antiulcer agents (2,15,16). However, to date no single agent has consistently displayed the capability to eradicate H. pylori from the gastric and duodenal mucosa for prolonged periods of time.…”

mentioning

confidence: 99%

Effect of omeprazole on concentrations of clarithromycin in plasma and gastric tissue at steady state

Gustavson

Kaiser

Edmonds

et al. 1995

Antimicrob Agents Chemother

118

View full text Add to dashboard Cite

This study was conducted to determine (i) the effect of omeprazole on steady-state concentrations of clarithromycin and 14-(R)-hydroxyclarithromycin in plasma and gastric mucosa, (ii) the effect of clarithromycin on steady-state concentrations of omeprazole in plasma, and (iii) the effect of clarithromycin on the suppression of gastric acid secretion by omeprazole. Twenty healthy, Helicobacter pylori-negative male subjects completed this three-period, double-blind, randomized crossover study. In period 1, all subjects received 40 mg of omeprazole each morning for 6 days. Twenty-four-hour gastric pH monitoring took place on days ؊1 and 6. Pharmacokinetic sampling took place on day 6. In periods 2 and 3, subjects were randomly assigned to receive either 40 mg of omeprazole or omeprazole placebo daily for 6 days plus clarithromycin (500 mg) every 8 h for 5 days with a single 500-mg dose on day 6. Gastric tissue and mucus samples were obtained via endoscopy on day 5. Gastric pH monitoring and pharmacokinetic sampling took place on day 6. Two-week washout intervals separated the three study periods. Clarithromycin increased mean omeprazole area under the concentration-time curve from 0 to 24 h from 3.3 ؎ 2.0 to 6.3 ؎ 4.5 g ⅐ h/ml (P < 0.05) and harmonic mean half-life from 1.2 to 1.6 h (P < 0.05) but did not significantly alter the effect of omeprazole on gastric pH. Mean clarithromycin area under the concentration-time curve from 0 to 8 h increased from 22.9 ؎ 5.5 (placebo) to 26.4 ؎ 5.7 g ⅐ h/ml (omeprazole) (P < 0.05) when clarithromycin was administered with omeprazole. Analysis of variance revealed that mean concentrations of clarithromycin in tissue and mucus were statistically significantly higher when clarithromycin was given with omeprazole than when clarithromycin was given with placebo (P < 0.001). Mean maximum observed concentrations of clarithromycin in the gastric fundus increased from 20.8 ؎ 7.6 (placebo) to 24.3 ؎ 6.4 g/g (omeprazole), and those in the gastric mucus increased from 4.2 ؎ 7.7 (placebo) to 39.3 ؎ 32.8 g/g (omeprazole). Similar increases were observed for the 14-(R)-hydroxyclarithromycin. These results show that omeprazole increases concentrations of clarithromycin in gastric tissue and mucus and may provide a mechanism for synergy between clarithromycin and omeprazole that explains the excellent eradication of H. pylori seen in clinical trials.Helicobacter pylori infection has been associated with gastritis, duodenal ulcers, gastric ulcers, and nonulcer dyspepsia. Approximately 85 to 100% of all duodenal ulcers and 70 to 90% of all gastric ulcers are associated with H. pylori infection in the stomach (19). Evidence suggests that eradication of H. pylori is associated with faster healing and a significant decrease in peptic ulcer recurrence (18). Previous studies have demonstrated the susceptibility of H. pylori to various antibiotics or antiulcer agents (2, 15, 16). However, to date no single agent has consistently displayed the capability to eradicate H. pylori from the gastric and duod...

show abstract

mentioning

confidence: 99%

Effect of omeprazole on concentrations of clarithromycin in plasma and gastric tissue at steady state

Gustavson

Kaiser

Edmonds

et al. 1995

Antimicrob Agents Chemother

118

View full text Add to dashboard Cite

show abstract

“…The treatment of gastric disease associated with H. pylon requires determination of the best therapeutic regimen by using proton pump inhibitors and antibiotics. The in vitro efficacy of clarithromycin against H. pylon (13,17,21) suggested its possible efficacy in vivo, and the results of initial clinical trials have been positive (4,11,24).…”

mentioning

confidence: 99%

Tight binding of clarithromycin, its 14-(R)-hydroxy metabolite, and erythromycin to Helicobacter pylori ribosomes

Goldman

Zakula

Flamm

et al. 1994

Antimicrob Agents Chemother

View full text Add to dashboard Cite

Clarithromycin is a recently approved macrolide with improved pharmacokinetics, antibacterial activity, and efficacy in treating bacterial infections including those caused by Helicobacter pylori, an agent implicated in various forms of gastric disease. We successfully isolated ribosomes from H. pylorz and present the results of a study of their interaction with macrolides. Kinetic data were obtained by using '4C-labeled macrolides to probe the ribosomal binding site. Clarithromycin, its parent compound erythromycin, and its 14-(R)-hydroxy metabolite all bound tightly to H. pylori ribosomes. Kd values were in the range of 2 x 10-10 M, which is the tightest binding interaction observed to date for a macrolide-ribosome complex. This tight binding was due to very slow dissociation rate constants of 7.07 x 10", 6.83 x 10-4, and 16.6 x 10-4 min-' for clarithromycin, erythromycin, and 14-hydroxyclarithromycin, respectively, giving half-times of dissociation ranging from 7 to 16 h, the slowest yet measured for a macrolide-ribosome complex. These dissociation rate constants are 2 orders of magnitude slower than the dissociation rate constants of macrolides from other gram-negative ribosomes.[14C]clarithromycin was bound stoichiometrically to 50S ribosomal subunits following incubation with 70S ribosomes and subsequent separation of the 30S and 50S subunits by sucrose density gradient centrifugation. These data predict that the lower MIC of clarithromycin compared with that of erythromycin for H. pylori is likely due to a faster rate of intracellular accumulation, possibly because of increased hydrophobicity.

show abstract

“…[146,147] U sed as monotherapy, clarithromycin and its even more active 14-hydroxy metabolite proved to be the most successful of all antimicrobial compounds against H. pylori.l 112 ,1l3] The pharmacology of clarithromycin has been reviewed in depth recently.l148] Clarithromycin is more acid-stable than erythromycin, and has a high rate of absorption, independent of food administration, and reaches high tissue levels in gastric mucosa.l1 49 ] As with amoxicillin, raising the pH from 5.5 to 7.0 leads to a substantial decrease in MIC90 for the drug. [150] The excretion of all macrolides is mainly hepatobiliary, with approximately 30% being excreted via the urine. Disturbed liver function leads to increased renal excretion; dose adjustment is only necessary in patients with renal impairment.…”

Section: Macro/idesmentioning

confidence: 99%

A Risk-Benefit Assessment of Drugs Used in the Eradication of Helicobacter pylori Infection

Hackelsberger

Malfertheiner

1996

Drug Safety

View full text Add to dashboard Cite

Helicobacter pylori is the cause of chronic active gastritis and predisposes to peptic ulcer disease (PUD). Furthermore, H. pylori is linked to the pathogenesis of gastric lymphoma and gastric cancer. However, treatment of this infection has proven difficult. In the last decade, many antimicrobial compounds have been studied extensively as monotherapy as well as in combination with bismuth or acid-suppressive drugs. The individual drugs and the most important eradication regimens are discussed with special regard to their risks. In the past, highly complex multidrug regimens, fear of adverse effects and frequent eradication failures have hampered the broad acceptance of H. pylori-eradication therapies. Recently, new 1-week, low-dose combination regimens of 2 antibacterials with a proton pump inhibitor have consistently achieved eradication rates of 90% and more with an acceptably low rate of adverse effects. One week's standard triple therapy [tripotassium dicitrato bismuthate (or bismuth salicylate plus metronidazole plus tetracycline or amoxicillin) has been shown to be highly effective and tolerated better in combination with a proton pump inhibitor. This regimen is, however, more complex and has more adverse effects. Therefore, it is not recommended as first-line therapy. Equipped with these therapies physicians can now be strongly encouraged to use H. pylori eradication as the therapy of choice for patients with PUD and even extend this treatment to other H. pylori-associated disease conditions.

show abstract

Effect of pH variation on the susceptibility ofHelicobacter pylori to three macrolide antimicrobial agents and temafloxacin

Cited by 54 publications

References 12 publications

Effect of omeprazole on concentrations of clarithromycin in plasma and gastric tissue at steady state

Effect of omeprazole on concentrations of clarithromycin in plasma and gastric tissue at steady state

Tight binding of clarithromycin, its 14-(R)-hydroxy metabolite, and erythromycin to Helicobacter pylori ribosomes

A Risk-Benefit Assessment of Drugs Used in the Eradication of Helicobacter pylori Infection

Contact Info

Product

Resources

About