Erythromycin lacks colon prokinetic effect in children with functional gastrointestinal disorders: a retrospective study

Abstract

BackgroundMotilin, a peptide hormone has a direct excitatory effect on circular smooth muscle strips derived from the human colon. Reduced plasma motilin concentration has been reported in adults with chronic constipation. Erythromycin, a non-peptide motilin receptor agonist, induces phase 3 of the migrating motor complex (MMC) in the antro-duodenum and also reduces oro-cecal transit time. A pediatric study has reported an improvement in clinical symptoms of constipation following erythromycin administration, but the effect on colon motility in children has not been formally evaluated. We used colon manometry to study the effect of intravenous erythromycin lactobionate at 1 mg/kg on colon motiltiy in ten children.MethodsWe selected patients with normal antroduodenal and colon manometry studies that were performed simultaneously. All studies were performed for clinically indicated reasons. We quantified the effect of erythromycin on colon contraction by calculating the area under the curve (AUC).ResultsThe mean (SE of mean) AUC in the colon during the fasting, post-erythromycin and postprandial phases of the study was 2.1 mmHg/sec (0.35), 0.99 mmHg/sec (0.17) and 3.05 mmHg/sec (0.70) respectively. The AUC following erythromycin was significantly less compared to the fasting phase of the study (p < 0.01).ConclusionErythromycin lacks colon prokinetic effect in children with chronic constipation evaluated by colon manometry.

Motilin: towards a new understanding of the gastrointestinal neuropharmacology and therapeutic use of motilin receptor agonists

“…One suggestion is that motilin has been retained during evolution to help promote defecation of the hard faecal pellets, which follow the initial excretion and re-ingestion of partly digested faeces (Costa et al, 1997;Sanger et al, 2009). Such activity contrasts with that in humans where the effects of motilin agonists on lower bowel functions have been found to vary (Jameson et al, 1992;Sharma et al, 1995;Bassotti et al, 1998;Emmanuel et al, 2004;Venkatasubramani et al, 2008).…”

Effect of intravenous erythromycin on the colonic motility of children and young adults during colonic manometry

“…Most recently, in the first pediatric study on this subject, Venkatasubramani et al [17] showed that 1 mg/kg of IV EL infused during colonic manometry failed to increase the MI 60 minutes after infusion in 10 children with normal colonic manometry; their study was limited by its small number, retrospective nature, and relatively low doses of EL. Similar to Venkatasubramani et al [17], we chose to evaluate colonic motility by full colonic manometry, as we believe this to be the most objective and detailed method of documenting motility. Our study builds on the study by Venkatasubramani et al [17] by its larger number, prospective design, higher dose of EL, and inclusion of patients with both normal and abnormal manometry.…”

“…Similar to Venkatasubramani et al [17], we chose to evaluate colonic motility by full colonic manometry, as we believe this to be the most objective and detailed method of documenting motility. Our study builds on the study by Venkatasubramani et al [17] by its larger number, prospective design, higher dose of EL, and inclusion of patients with both normal and abnormal manometry.…”

“…Building on this knowledge, motilin receptors were found in similar concentrations in the colon as in the stomach and duodenum, sparking further interest in erythromycin's possible use as a colokinetic agent [15,16]. Recently, Venkatasubramani et al [17] retrospectively studied 10 children undergoing antroduodenal and colonic manometry and noted a significant decrease in MI 60 minutes after administration of 1 mg/kg of intravenous (IV) erythromycin; they concluded that further studies at higher doses of erythromycin were needed. Given the current gaps in the knowledge, we aimed to study the effect of erythromycin on the colonic motility of children and young adults undergoing colonic manometry by comparing colonic MI before and after administration of IV erythromycin lactobionate (EL).…”

Drugs Acting on the Gut: Prokinetics, Antispasmodics, Laxatives

“…Long-term therapy appears to be safe; however, decreased ef fi cacy is seen after prolonged treatment due to downregulation of motilin receptors. There has been no evidence that erythromycin has any prokinetic effect on the colon as shown by administration of the drug during colonic manometry studies [ 36,37 ] .…”