Dose-Related Stimulatory Effect of Clarithromycin on Interdigestive Gastroduodenal Motility

Abstract

Background/Aims: The effect on interdigestive gastroduodenal motility of different doses of clarithromycin, an antibiotic commonly used for Helicobacter pylori eradication, has been investigated. Methods: Gastroduodenal motility was recorded by means of a low-compliance manometric system in 15 healthy subjects. Thirty minutes after the first phase III of the migrating motor complex, clarithromycin (CLA) was infused intravenously at a dose of 100 mg in 5, 250 mg in 5 and 400 mg in 5 subjects, randomly and in a double-blind manner, continuing the recording for at least 1 h. A further study was carried out on 10 subjects, 5 of whom received 50 mg CLA and 5 normal saline with the same modalities. Results: After 100 mg CLA a premature gastroduodenal phase III ensued in all cases, which showed a duration, propagation velocity and wave frequency not significantly different from the spontaneous one and was followed by a clear phase I. A premature gastroduodenal phase-III-like activity occurred in 3 cases of 250 mg CLA and 2 cases after 400 mg CLA, followed by a very short or absent phase I and characterized by a long duration of the antral phase III, while in the remaining cases a long-lasting sequence of about 1/min of antral waves propagated to the duodenum appeared, sometimes preceded by an antral phase-III-like activity not propagated to the duodenum. After 50 mg CLA a premature phase III appeared in 2 cases, while a not premature phase III appeared in 2 cases after saline. Conclusion: CLA shows a dose-related stimulatory effect on interdigestive gastroduodenal motility varying from the initiation of a typical phase III to a prolonged sequence of gastroduodenal coordinated waves. These motor effects of CLA suggest potential therapeutic applications.

Variable abnormal physiological motility in the proximal upper gastrointestinal tract in gastroparesis

“…However, disruption of this relationship may play an important role in the pathogenesis of gastroparesis. Clinically, this may have an impact on therapy as the pharmacological dosing in the treatment of small bowel dysmotility is typically less aggressive compared to gastric stimulation with a motilide agent (40, 41). …”

Interdisciplinary Science and the Design of a Single-Dose Antibiotic Therapy

“…In the case of azithromycin, it is possible that GI side effects are pharmacologically mediated in the GI wall because the drug has been reported to bind to the human gastric antrum motilin receptor (55). The macrolides clarithromycin and erythromycin also bind to this receptor (55) and are known to affect GI motility (56,57). However, the motilin receptor is expressed throughout the GI tract (58,59), and the relationship is not clear between motilin receptor density and the observed site-specific GI sensitivity to azithromycin.…”

Effect of clarithromycin on esophageal motility

“…Thirty minutes after the occurence of a duodenal phase III, we infused intravenously, randomly, and in a double‐blind manner, CLA 100 mg in five subjects (group A), CLA 250 mg in five subjects (group B) and normal saline in the remaining five subjects (group C). We chose the dosage of 100 mg because it was the lowest dosage that stimulated phase III activity in all subjects in a previous study 10 . The analysis of recordings was performed by an investigator unaware of the substance administered.…”