Metoclopramide in the treatment of diabetic gastroparesis

Lee, Allen; Kuo, Braden

doi:10.1586/eem.10.41

Cited by 89 publications

(67 citation statements)

References 80 publications

(92 reference statements)

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…These side effects are more likely to be associated with high doses, intravenous administration, and prolonged usage. 33 Dystonic reactions, including oculogyric crises, are most likely to occur within a few days of treatment and are more common in young patients although they have also been reported in older females. 15 Drug-induced Parkinsonism and tardive dyskinesia are associated with long-tem drug usage, usually >3 months.…”

Section: Discussionmentioning

confidence: 99%

“…Other side effects, such as confusion, diarrhea, cardiac arrhythmias, and hyperprolactinemia, are fully reversible with discontinuation of metoclopramide. 33 It is possible that limiting the maximum dose to 10 mg 3× a day was safe and did not produce toxic levels that would have produced early dystonic reactions and that limiting the use of metoclopramide to a maximum of 3 weeks prevented manifestation of side effects associated with long-term use. Our findings suggest that metoclopramide in the doses and duration used in the MAPS trial seems to be safely used in this patient population.…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Safety and Effect of Metoclopramide to Prevent Pneumonia in Patients With Stroke Fed via Nasogastric Tubes Trial

Warusevitane

Karunatilake

Sim

et al. 2015

Stroke

View full text Add to dashboard Cite

Background and Purpose— Pneumonia is a major cause of mortality and morbidity in patients with stroke fed via nasogastric tubes and may be because of vomiting and gastro-oesophageal regurgitation. The aim of the study was to assess whether regular treatment with metoclopramide, a D2-receptor antagonist with antiemetic and gastric prokinetic actions, could reduce the rate of aspiration and pneumonia. Methods— Patients with no signs of pneumonia within 7 days of stroke onset and 48 hours of insertion of a nasogastric tube were recruited into a double-blind randomized placebo-controlled trial. Participants received metoclopramide 10 mg or placebo 3× daily via the nasogastric tube for 21 days or until nasogastric feeds were discontinued. Clinical signs of pneumonia were recorded daily. Pneumonia was diagnosed if the patient had relevant clinical signs, high inflammatory markers, and new infiltrates on the chest radiograph. Results— Sixty patients (mean age, 78 years; 38 women; mean National Institutes for Health Stroke Scale score, 19.25) were randomized in a 1:1 ratio. There were significantly more episodes of pneumonia in the placebo group than in the metoclopramide group (rate ratio, 5.24; P <0.001). There were also significant differences in favor of metoclopramide in the rate of aspiration, oxygen saturation, highest inflammatory markers, and National Institutes for Health Stroke Scale. There was no significant difference in mortality between the groups. Conclusions— This study suggests that metoclopramide may reduce the rate of pneumonia and may improve other clinical outcomes in patients with subacute stroke fed via nasogastric tube. These findings need to be confirmed in larger randomized and blinded trials. Clinical Trial Registration— URL: https://www.clinicaltrialsregister.eu . EudraCT no: 2006-002570-22, URL: http://www.controlled-trials.com/ISRCTN18034911/18034911 .

show abstract

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Safety and Effect of Metoclopramide to Prevent Pneumonia in Patients With Stroke Fed via Nasogastric Tubes Trial

Warusevitane

Karunatilake

Sim

et al. 2015

Stroke

View full text Add to dashboard Cite

show abstract

“…Metoclopramide intravenous formulation is commonly prescribed as an antiemetic (14). In patients, reported effects of metoclopramide on the CNS suggest substantial baseline brain distribution (14).…”

mentioning

confidence: 99%

Imaging the Impact of the P-Glycoprotein (ABCB1) Function on the Brain Kinetics of Metoclopramide

Pottier¹,

Marie²,

Goutal³

et al. 2015

J Nucl Med

105

View full text Add to dashboard Cite

The effects of metoclopramide on the central nervous system (CNS) in patients suggest substantial brain distribution. Previous data suggest that metoclopramide brain kinetics may nonetheless be controlled by ATP-binding cassette (ABC) transporters expressed at the blood-brain barrier. We used 11 C-metoclopramide PET imaging to elucidate the kinetic impact of transporter function on metoclopramide exposure to the brain. Methods: 11 C-metoclopramide transport by P-glycoprotein (P-gp; ABCB1) and the breast cancer resistance protein (BCRP; ABCG2) was tested using uptake assays in cells overexpressing P-gp and BCRP. 11 C-metoclopramide brain kinetics were compared using PET in rats (n 5 4-5) in the absence and presence of a pharmacologic dose of metoclopramide (3 mg/kg), with or without P-gp inhibition using intravenous tariquidar (8 mg/kg). The 11 C-metoclopramide brain distribution (V T based on Logan plot analysis) and brain kinetics (2-tissue-compartment model) were characterized with either a measured or an imaged-derived input function. Plasma and brain radiometabolites were studied using radio-high-performance liquid chromatography analysis. Results: 11 C-metoclopramide transport was selective for P-gp over BCRP. Pharmacologic dose did not affect baseline 11 C-metoclopramide brain kinetics (V T 5 2.28 ± 0.32 and 2.04 ± 0.19 mL⋅cm −3 using microdose and pharmacologic dose, respectively). Tariquidar significantly enhanced microdose 11 C-metoclopramide V T (7.80 ± 1.43 mL⋅cm −3 ) with a 4.4-fold increase in K 1 (influx rate constant) and a 2.3-fold increase in binding potential (k 3 /k 4 ) in the 2-tissue-compartment model. In the pharmacologic situation, P-gp inhibition significantly increased metoclopramide brain distribution (V T 5 6.28 ± 0.48 mL⋅cm −3 ) with a 2.0-fold increase in K 1 and a 2.2-fold decrease in k 2 (efflux rate), with no significant impact on binding potential. In this situation, only parent 11 C-metoclopramide could be detected in the brains of P-gp-inhibited rats. Conclusion: 11 C-metoclopramide benefits from favorable pharmacokinetic properties that offer reliable quantification of P-gp function at the blood-brain barrier in a pharmacologic situation. Using metoclopramide as a model of CNS drug, we demonstrated that P-gp function not only reduces influx but also mediates the efflux from the brain back to the blood compartment, with additional impact on brain distribution. This PET-based strategy of P-gp function investigation may provide new insight on the contribution of P-gp to the variability of response to CNS drugs between patients.

show abstract

“…10 Metoclopramide is metabolized mainly by CYP2D6 and to a lesser extent by the CYP3A4 and CYP1A3 11 ; up to 30% of the drug is excreted unchanged in the urine. 12 Mechanism of action Metoclopramide has dual activity as a D2 receptor antagonist and a 5-HT 4 agonist, decreasing effects of dopamine and thereby stimulating the cholinergic receptors.…”

Section: Metoclopramidementioning

confidence: 99%