Domperidone Treatment for Gastroparesis: Demographic and Pharmacogenetic Characterization of Clinical Efficacy and Side-Effects

@article{Parkman2010DomperidoneTF,
  title={Domperidone Treatment for Gastroparesis: Demographic and Pharmacogenetic Characterization of Clinical Efficacy and Side-Effects},
  author={Henry P. Parkman and Michael R. Jacobs and Anurag K. Mishra and Jessica A. Hurdle and Priyanka Sachdeva and J Gaughan and Evgeny Krynetskiy},
  journal={Digestive Diseases and Sciences},
  year={2010},
  volume={56},
  pages={115-124}
}
BackgroundDomperidone is a useful alternative to metoclopramide for treatment of gastroparesis due to better tolerability. Effectiveness and side-effects from domperidone may be influenced by patient-related factors including polymorphisms in genes encoding drug-metabolizing enzymes, drug transporters, and domperidone targets.AimsThe aim of this study was to determine if demographic and pharmacogenetic parameters of patients receiving domperidone are associated with response to treatment or… 
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Polymorphisms in CYP2D6, KC NH2, and 5-HT4 receptor HTR4 genes were associated with side effects, whereas polymorphisms in KCNH2 and ADRA1D genes wereassociated with clinical response.
Effect of Domperidone Therapy on Gastroparesis Symptoms: Results of a Dynamic Cohort Study by NIDDK Gastroparesis Consortium.
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Clinical symptom scores combined with real-time ultrasonography is effective in evaluating the therapeutic effect of domperidone in patients with functional dyspepsia, and the therapeutic result was associated with polymorphism of dopamine D2 receptor TaqI gene.
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The majority of patients remaining on treatment with domperidone experienced an improvement in symptoms of gastroparesis, particularly postprandial fullness, nausea, vomiting, and stomach fullness.
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Cardiotoxic Antiemetics Metoclopramide and Domperidone Block Cardiac Voltage-Gated Na+ Channels
TLDR
The data demonstrate that the clinically relevant cardiotoxicity of domperidone and metoclopramide corresponds to a rather potent and local anesthetic-like inhibition of cardiac Na+ channels including Nav1.5, which might be a hitherto unrecognized molecular mechanism of some cardiovascular side effects, for example, malignant arrhythmias of prokinetic and antiemetic agents.
Identification of domperidone metabolites in plasma and urine of gastroparesis patients with LC–ESI-MS/MS
TLDR
12 domperidone metabolites including 7 new metabolites were identified including 5 additional metabolites which comprise two additional mono-hydroxylated metabolites, an alcohol metabolite possibly formed from an aldehyde intermediate, and other conjugative metabolites (M6, M10 and M12).
Clinical implications of neuropharmacogenetics.
Domperidone in Parkinson's disease: a perilous arrhythmogenic or the gold standard?
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Despite domperidone being recognized as the first choice for treating gastrointestinal symptoms PD, doses above 30 mg/daily should only be considered with special caution taking into account its potential cardiotoxic effects.
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References

SHOWING 1-10 OF 42 REFERENCES
Comparative evaluation of the efficacy and tolerability of itopride hydrochloride and domperidone in patients with non-ulcer dyspepsia.
BACKGROUND Prokinetic drugs are widely used for treatment of non-ulcer dyspepsia (NUD). AIMS AND OBJECTIVES To assess the efficacy and tolerability of a new prokinetic agent, itopride hydrochloride
Role of a KCNH2 polymorphism (R1047 L) in dofetilide-induced Torsades de Pointes.
Pharmacogenetics/genomics and personalized medicine.
Despite the marked advances in drug therapy, some patients do not respond favorably or suffer severe adverse drug effects. Pharmacogenetic studies have shown that polymorphisms of drug metabolizing
The missing linkage: what pharmacogenetic associations are left to find in CYP3A?
  • M. Perera
  • Biology
    Expert opinion on drug metabolism & toxicology
  • 2010
TLDR
More innovative and comprehensive methods to assay this region are needed, with particular attention paid to the role of gene regulation and non-coding sequence.
Polymorphisms of norepinephrine transporter and adrenergic receptor alpha1D are associated with the response to beta-blockers in dilated cardiomyopathy.
TLDR
Genotyping of 39 polymorphisms in 16 genes related to adrenergic system may provide clinical insights into an individual difference in the response to the beta-blocker therapy in CHF and suggest that NET (T-182C) and ADRA1D (T1848A and A1905G) polymorphisms are predictive markers of the response.
Substrate-Dependent Effects of Human ABCB1 Coding Polymorphisms
TLDR
Functional data demonstrate that nonsynonymous polymorphisms in ABCB1 may selectively alter P-gp transport and drug-drug interactions in a substrate- and inhibitor-dependent manner.
A synonymous polymorphism in a common MDR1 (ABCB1) haplotype shapes protein function.
Identification of the cytochrome P450 enzymes involved in the metabolism of domperidone
TLDR
The data suggest that CYP3As are the major enzymes involved in the metabolism of domperidone.
...
1
2
3
4
5
...