Related Experiment Videos
Dose-response study of metoclopramide in gastroesophageal reflux in infancy
G Pons1, J F Duhamel, M Guillot
1Département de Pharmacologie Clinique Périnatale et Pédiatrique, Hôpital Saint-Vincent-de-Paul, Paris, France.
Insights
Metoclopramide showed potential in reducing esophageal acid exposure in infants with gastroesophageal reflux, though results varied. Further studies on repeated dosing are recommended for this infant reflux treatment.
Area of Science:
- Pediatric Gastroenterology
- Clinical Pharmacology
Background:
- Gastroesophageal reflux is a common concern in infants.
- Accurate assessment of esophageal pH is crucial for diagnosis and treatment monitoring.
Purpose of the Study:
- To evaluate the dose-response relationship of metoclopramide in infants with confirmed gastroesophageal reflux.
- To assess the efficacy of single-dose metoclopramide on esophageal acid exposure.
Main Methods:
- A double-blind, placebo-controlled trial involving 24 infants (1-18 months) with gastroesophageal reflux.
- Infants received placebo or single doses of metoclopramide (0.1, 0.2, 0.4 mg/kg) before formula meals on consecutive days.
- Esophageal pH monitoring and metoclopramide plasma concentration (C1h) were measured.
Main Results:
- No significant differences in esophageal acid exposure were observed between metoclopramide groups and placebo on day 2.
- Esophageal acid exposure decreased significantly as a function of plasma metoclopramide concentration (C1h).
- No adverse effects were reported during the study.
Conclusions:
- Single-dose metoclopramide did not show a significant dose-dependent effect on esophageal acid exposure in infants.
- Plasma concentration of metoclopramide correlated with reduced esophageal acid exposure, suggesting potential efficacy.
- Further investigation with a repeated dosing regimen is warranted to confirm the therapeutic potential of metoclopramide in infant gastroesophageal reflux.
Abstract:
Twenty-four infants, 1 to 18 months-old, who were referred to four centers for suspected gastroesophageal reflux and whose esophageal pH after a standard formula meal given at 9 to 10 am (Ho-day 1) fulfilled the criterion of being < 4 for more than 5% of the time between H1 and H6, entered a double-blind placebo-controlled dose-response trial of metoclopramide (M). Twenty-four hours later (day 2), patients were randomly assigned to receive either placebo or a single 0.1, 0.2, or 0.4 mg/kg dose of metoclopramide, 30 min before the formula meal (n = 6/group) and the procedure was repeated. Metoclopramide plasma concentration was measured 1 h after dosing (C1h). On day 1, the time during which the esophageal pH was < 4 (time pH < 4), and five other parameters, were not significantly different in the treatment groups. On day 2, time pH < 4 (m(SD)) decreased from 33(13) to 30(33), 39(27), to 36(47), 42(15) to 18(13) and 48(25) to 31(46) min in the placebo, 0.1, 0.2, and 0.4 mg/kg metoclopramide groups, respectively. Possibly due to the large interindividual variability, no significant differences in parameters were observed between the different groups. None of the parameters correlated with the metoclopramide dose. Time pH < 4 expressed as the difference between day 1 and day 2, relative to day 1, decreased significantly as a function of C1h. No side effects were observed. A similar study should be performed after repeated dosing regimen.