Erythromycin Accelerates Gastric Emptying in a Dose-Response Manner in Healthy Subjects

Michel A. Boivin, MD; Michael C. Carey, BS; Howard Levy, MD, Ph.D.

Disclosures

Pharmacotherapy. 2003;23(1) 

In This Article

Abstract and Introduction

Study Objectives: To evaluate whether a dose-response curve exists for erythromycin, determine the lowest effective dose of erythromycin needed to improve gastric motility, and compare erythromycin's effectiveness with that of metoclopramide in improving gastric emptying.
Design: Randomized, crossover, multiintervention trial.
Setting: Inpatient clinical research center.
Subjects: Ten healthy volunteers (four men, six women) from the general population.
Intervention: On each study day, the subjects were infused with erythromycin 0.75 mg/kg, 1.5 mg/kg, or 3.0 mg/kg; metoclopramide 10 mg; or placebo, in random order. Subjects then drank Ensure 200 ml mixed with acetaminophen 1.5 g. Gastric emptying was estimated by comparing the area under the curve after 60 minutes for acetaminophen absorption using four timed blood draws.
Measurements and Main Results: Erythromycin increased gastric emptying in a dose-response manner. Erythromycin 3.0 mg/kg and metoclopramide 10 mg were associated with statistically significant increases in liquid gastric emptying compared with placebo. During infusion, nausea and stomach cramping were associated with the 3.0-mg/kg dose of erythromycin; drowsiness was associated with metoclopramide.
Conclusion: In patients requiring intravenous erythromycin for gastric motility, the 3.0-mg/kg dose seems the most effective, with a reasonable side effect profile.

Gastric emptying is frequently abnormal in patients with critical illness.[1,2] Returning this function to normal is essential in order to provide these patients with adequate nutrition. In the United States, two agents are available for treatment of slow gastric emptying (gastroparesis): erythromycin and metoclopramide.

Most clinical studies have administered erythromycin in doses of 2-3 mg/kg.[3,4,5] However, the minimum dose of erythromycin that accelerates gastric emptying in humans is not known, although doses above 0.5 mg/kg cause increased gastric muscle movements.[6,7] This is relevant because the side effects associated with erythromycin (nausea, vomiting, and diarrhea) appear to be dose dependent.[7] Doses as high as 1000 mg have been studied, and although side effects increased with higher doses, gastric emptying did not improve when compared with a 250-mg dose.[8] Whether a dose lower than 250 mg (approximately 3 mg/kg) would be just as effective is unknown. Erythromycin increases gastric emptying by acting as an agonist on the motilin receptor in smooth gastrointestinal muscle. Although the side effects commonly attributed to erythromycin occur in only 7-10% of patients given oral erythromycin,[7] their occurrence with intravenous erythromycin is much higher.[7]

Metoclopramide is a promotility agent that is commonly prescribed for critically ill patients.[1] It acts by blocking dopamine receptors in the gastrointestinal tract, thereby allowing the stimulatory acetylcholine to be dominant. Metoclopramide also crosses the blood-brain barrier and acts as an antiemetic by blocking the dopamine receptors in the central nervous system. Central nervous system side effects, such as restlessness, drowsiness, fatigue, and lassitude, usually are mild. Particularly worrisome are the extrapyramidal symptoms, such as dystonic reactions and Parkinson-like symptoms; however, these are rare.[9] The relative potency of metoclopramide compared with that of erythromycin is not known.

One method of studying gastric emptying is by acetaminophen absorption. Since acetaminophen is absorbed only in the duodenum and small intestine and not the stomach, absorption is related to the rate of gastric emptying. Studies have compared gastric emptying assessed by scintigraphic methods (considered the gold standard) versus the acetaminophen absorption method.[10] The goal of one such study was to determine the extent of intersubject and intrasubject variability in the gastric emptying of semisolid liquid meals using the acetaminophen absorption method and comparing it with the scintigraphic method.[10] Intrasubject acetaminophen emptying correlated highly with liquid emptying of the stomach by scintigraphic methods, thus acetaminophen emptying is an ideal assay for repeated comparisons.[10,11,12,13]

Our study was designed to determine the lowest effective dose of erythromycin needed to improve gastric motility and to compare its effectiveness with that of the usual dose of metoclopramide. In addition, we compared the subjective side effects of erythromycin with those of metoclopramide using a standard Likert scale.[14]

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