Identification of the cytochrome P450 enzymes involved in the metabolism of domperidone

@article{Simard2004IdentificationOT,
  title={Identification of the cytochrome P450 enzymes involved in the metabolism of domperidone},
  author={Chantale Simard and Veronique Michaud and Brian Gibbs and Robert Mass{\'e} and {\'E}tienne Lessard and Jacques Turgeon},
  journal={Xenobiotica},
  year={2004},
  volume={34},
  pages={1013 - 1023}
}
1. The objective was to identify the major cytochrome P450 enzyme(s) involved in the metabolism of domperidone. 2. Experiments were performed using human liver microsomes (HLMs), recombinant human cytochrome P450 enzymes, cytochrome P450 chemical inhibitors and monoclonal antibodies directed against cytochrome P450 enzymes. 3. Four metabolites were identified from incubations performed with HLMs and excellent correlations were observed between the formation of domperidone hydroxylated… 
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An improved HPLC assay with fluorescence detection for the determination of domperidone and three major metabolites for application to in vitro drug metabolism studies.
  • V. Michaud, C. Simard, J. Turgeon
  • Chemistry, Biology
    Journal of chromatography. B, Analytical technologies in the biomedical and life sciences
  • 2007
Metabolic interactions between prokinetic agents domperidone and erythromycin: an in vitro analysis
TLDR
This study examined in vitro interaction between domperidone and erythromycin, prescribed for refractory gastroparesis, and predicted greater dom peridone drug exposure when used with erystromycin.
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).
Domperidone interacts with pioglitazone but not with ondansetron via common CYP metabolism in vitro
TLDR
In vitro data predict that the co-administration of these drugs can potentially trigger an in vivo drug–drug interaction and pioglitazone inhibited domperidone metabolism in vitro through different complex mechanisms.
Modulation of CYP3a expression and activity in mice models of type 1 and type 2 diabetes
TLDR
The results suggest that these two distinct diseases may have the same modulating effect on the regulation of CYP3a, ultimately leading to variability in drug response, ranging from lack of effect to life‐threatening toxicity.
Elucidation of in vitro phase I metabolites of droperidol using UPLC-QTOF MS
TLDR
The phase I metabolism of droperidol was investigated using ultra-performance liquid chromatography–quadrupole time-of-flight mass spectrometry, and five new metabolites were identified.
Physiologically based predictions of the impact of inhibition of intestinal and hepatic metabolism on human pharmacokinetics of CYP3A substrates.
TLDR
The ability of the PBPK model to predict DDI of CYP3A substrates with promising accuracy was demonstrated, and the impact of DHB-mediated inhibition on the extent of intestinal pre-systemic elimination of MDZ and SMV has been accurately predicted by the proposed P BPK model.
Prediction of pharmacokinetic drug-drug interaction caused by changes in cytochrome P450 activity using in vivo information.
Drug-induced changes in P450 enzyme expression at the gene expression level: A new dimension to the analysis of drug–drug interactions
TLDR
It is proposed that the well-documented, but poorly understood, increase in incidence of rhabdomyolysis when a PPAR α agonist is co-administered with a HMG-CoA reductase inhibitor is at least in part the result of PPARα-induced general suppression of drug metabolism enzymes in liver.
Decreased CYP3A Expression and Activity in Guinea Pig Models of Diet-Induced Metabolic Syndrome: Is Fatty Liver Infiltration Involved?
TLDR
Diet-induced metabolic syndrome decreases CYP3A expression/activity in guinea pigs, which may ultimately lead to variability in drug response, ranging from lack of effect to life-threatening toxicity.
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References

SHOWING 1-10 OF 14 REFERENCES
Cytochrome P450 inhibitors. Evaluation of specificities in the in vitrometabolism of therapeutic agents by human liver microsomes.
TLDR
Nine chemical inhibitors were selected based on literature data and were examined for their specificity toward cytochrome P450-mediated reactions in human liver microsomes and troleandomycin proved to be the most specific for testosterone 6 beta-hydroxylation.
Involvement of CYP2D6 activity in the N-oxidation of procainamide in man.
TLDR
The results suggest that CYP2D6 is involved in the in-vivo aliphatic amine deethylation and N-oxidation of procainamide at its arylamine function in man.
Ketoconazole and sulphaphenazole as the respective selective inhibitors of P4503A and 2C9.
TLDR
Ketoconazole and sulphaphenazole can be used to establish the involvement of P4503A and 2C9 respectively in oxidative reactions in human liver microsomes and demonstrate an inhibitory effect on cyclosporine oxidase and testosterone 6 beta-hydroxylase activities.
Genetic polymorphism of cytochrome P450 3A5 in Chinese.
TLDR
It is found that 28% of CYP3AP1 alleles are G(-44) in 110 Chinese subjects, the frequency is 3 times higher in Chinese than in Caucasian, implying more Chinese subjects are probably extensive CYP 3A5 metabolizers.
Sequence diversity in CYP3A promoters and characterization of the genetic basis of polymorphic CYP3A5 expression
TLDR
CYP3A5 was more frequently expressed in livers of African Americans than in those of Caucasians, and may be the most important genetic contributor to interindividual and interracial differences in CYP3A-dependent drug clearance and in responses to many medicines.
Domperidone: A Peripherally Acting Dopamine2-Receptor Antagonist
  • J. Barone
  • Medicine, Psychology
    The Annals of pharmacotherapy
  • 1999
TLDR
In controlled clinical trials, domperidone provided better relief of symptoms than placebo in patients with symptoms of diabetic gastroparesis and prevented the gastrointestinal and emetic adverse effects of antiparkinsonian drugs.
Domperidone. A review of its pharmacological activity, pharmacokinetics and therapeutic efficacy in the symptomatic treatment of chronic dyspepsia and as an antiemetic.
TLDR
Alleviation of the dose-limiting peripheral side effects of the anti-Parkinsonian drugs bromocriptine and levodopa, enables a higher optimum dose, with consequent improvement in Parkinsonian symptoms.
Domperidone Should Not Be Considered a No-Risk Alternative to Cisapride in the Treatment of Gastrointestinal Motility Disorders
TLDR
Domperidone possesses cardiac electrophysiological effects similar to those of cisapride and class III antiarrhythmic drugs, and should not be considered a no-risk alternative to cisAPride, a drug that was recently withdrawn from the US market.
Domperidone. A review of its use in diabetic gastropathy.
TLDR
The available data suggest that domperidone 40 to 80 mg/day is an effective agent for the management of symptoms of gastropathy in patients with type 1 diabetes mellitus and may provide symptom improvement in Patients with Gastropathy refractory to other gastroprokinetic agents.
Cardiac Arrhythmias during Cytotoxic Chemotherapy: Role of Domperidone
TLDR
Treatment with intravenous domperidone is associated with the occurrence of cardiac arrhythmias in patients receiving platinum-containing chemotherapy and a control group of 14 patients treated with similar chemotherapy also underwent cardiac and plasma potassium monitoring.
...
1
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