Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.2.1.31 (beta-glucuronidase)
 7,680 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Identifying individuals with a deficient capacity for oxidative drug metabolism is of increasing clinical importance. Dextromethorphan (DM) is gaining wide acceptance as a probe drug to characterize individual expression of a specific cytochrome P-450 isozyme. The thin-layer chromatography (TLC) technique described in the present study is a rapid and inexpensive alternative to the methods currently available for assessing the urinary metabolic profile of DM. Sixty-five healthy volunteers participated in the study by ingesting 213 mmol DM and collecting all urine for the ensuing 8 h. Urine samples were analyzed by TLC and high-performance liquid chromatography (HPLC) after treatment with beta-glucuronidase. Based on the relative color intensities of DM and its O-demethylated metabolite, dextrorphan, the TLC analysis provided an accurate phenotype assessment. A greater intensity of the parent drug relative to the metabolite indicates a poor metabolizer phenotype whereas a reversed relative intensity indicates the extensive metabolizer phenotype. The phenotype assignments made by TLC were verified by comparison with the quantitative results (based on metabolic ratios) obtained from HPLC analysis. Complete agreement was found between the two methods. The routine implementation of phenotype determination into clinical protocols can be realized with this facile TLC technique.
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PMID:Simplified phenotyping with dextromethorphan by thin-layer chromatography: application to clinical laboratory screening for deficiencies in oxidative drug metabolism. 320 36

Dextromethorphan (DEM) is a widely used probe drug for human cytochrome P450 2D6 isozyme activity assessment by measuring the ratio between DEM and its N-demethylated metabolite dextrorphan (DOR). DOR is excreted in urine mainly conjugated to glucuronic acid. Prior to quantification, DOR must be deconjugated to avoid variability caused by the polymorphic glucuronosyltransferase enzyme. A chemical hydrolysis method was optimized using a chemometric approach. Three factors (acid concentration, hydrolysis time and temperature) were selected and simultaneously varied to study their effect on conjugated DOR hydrolysis. Hydrolysis conditions that maximize DOR release without significant degradation of both DEM and DOR were chosen and results were compared to those obtained by enzymatic method using beta-glucuronidase. An HPLC method with fluorescence detection was developed for the simultaneous quantitation of DEM, DOR and levallorphan, used as an internal standard. Separation was performed on a phenyl analytical column (150 mmx4.6 mm i.d., 5 microm) with a mobile phase consisting of 18% acetonitrile and 50 mM phosphoric acid (pH 3). The overall analytical procedure was validated and showed good performances in terms of selectivity, linearity, sensitivity, precision and accuracy. Finally, this assay was used to determine DEM/DOR molar ratios in fibromyalgia patients for the purpose of determining phenotype status for the CYP2D6.
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PMID:Development and validation of a chemical hydrolysis method for dextromethorphan and dextrophan determination in urine samples: application to the assessment of CYP2D6 activity in fibromyalgia patients. 1806 99