Erythromycin Lacks Colon Prokinetic Effect in Children With Constipation

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Abstract and Background

Abstract

Background: Motilin, 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.
Methods: We 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).
Results: The 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).
Conclusion: Erythromycin lacks colon prokinetic effect in children with chronic constipation evaluated by colon manometry.

Background

Constipation accounts for 3% of general pediatric and 10-20% of pediatric gastroenterology outpatient visits.^[1] A majority of these patients have functional constipation and the symptoms improve following behavioral modification and laxative treatment.^[2] Almost 30% of children with chronic constipation will have persistent symptoms or relapses that can persist into adult life.^[3] Children with chronic intractable constipation, who do not respond to conventional medical therapy, require manometric evaluation to exclude an underlying colon neuromuscular abnormality.

Motilin is a 22-amino acid peptide hormone secreted by the enterochromaffin cells of the small intestine.^[4,5] It exerts profound effect on gastric and small bowel motility by inducing the inter-digestive phase 3 of the migrating motor complex (MMC).^[6] Peak plasma concentration of motilin is associated with MMC, both in animals and humans.^[7,8,9]

Conflicting results exists regarding the erythromycin effect on circular smooth muscle strips derived from the human colon. Few studies have reported the stimulatory effect of erythromycin in human smooth muscle contractions^[10,11] and Nissan have reported lack of any excitatory effect on human colon.^[12] Studies have shown that motilin receptor is expressed in the enteric neurons of the colon^[10,13] and plasma motilin concentration is reduced in adults with chronic constipation.^[14] Oral and intravenous erythromycin has no effect on distal colon contraction or transit in healthy human volunteers.^[15]

Erythromycin is a non-peptide motilin receptor agonist which induces phase 3 of the migrating motor complex in the antro-duodenum. Several studies have reported that erythromycin is safe and effective in improving feeding intolerance in preterm infants and children.^{[16,17,18,19]} The prokinetic effect of erythromycin has also been reported in older children with motility disorders.^[20] The data regarding the colon prokinetic effect of erythromycin is controversial. Oral erythromycin has been shown to reduce the colonic transit time assessed using radio opaque markers in adults with chronic constipation.^[21] However, another adult study using colon manometry reported no significant improvement in colon motility with erythromycin compared to a placebo.^[22] To date, no studies have evaluated the effect of erythromycin on colon motility in children.

The aim of our study was to evaluate the effect of intravenous erythromycin lactobionate (1 mg/kg) on colon motility in children with chronic constipation and fecal incontinence using colon manometry.

This is an Open Access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

All authors read and approved the final manuscript.

Cite this: Erythromycin Lacks Colon Prokinetic Effect in Children With FunctionalGastrointestinal Disorders: A Retrospective Study - Medscape - Aug 21, 2008.

Table 1. AUC and HAPCs During Fasting, Following a Meal and Erythromycin
	Fasting Period	Postprandial period	Post-erythromycin period	Bisacodyl stimulation
Mean area under the curve in mm/sec (SE of mean)	2.1(0.35)	3.05 (0.70)	0.9 (0.17)	NA
Mean number of HAPCs (range)	0.4 (0-1)	0.00 (0)	0.1 (0-1)	8.9 (1-16)

The mean area under the pressure line during fasting, following a meal and erythromycin lactobionate administration. The mean number of HAPCs recorded during each of these periods and following bisacodyl stimulation are also shown

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