Quantitative Determination of Dextromethorphan and Three Metabolites in Urine by Reverse-Phase High-Performance Liquid Chromatography

Park, Young Han; Kullberg, Max; Hinsvark, O. N.

doi:10.1002/jps.2600730107

Cited by 79 publications

(31 citation statements)

References 6 publications

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“…All 17 patients from group 2 received both the ERMBT and the DUT using established methods. [22][23][24] intent of our study was to determine the clinical utility of the CBT, it seemed important to also assess the predictability The ERMBT has been shown to be a convenient means of estimating the activity of CYP3A4, 25 which is the most abunof the only commercially available CBT kit. This kit uses a standardized dose of 200 mg [ 13 C-3-methyl] caffeine.…”

Section: Methodsmentioning

confidence: 99%

The Caffeine Breath Test Does Not Identify Patients Susceptible to Tacrine Hepatotoxicity

et al. 1996

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position of the drug in vivo. (HEPATOLOGY 1996;23:1429-Therapy with tacrine, a promising new treatment for 1435.) Alzheimer's disease, must be discontinued in up to 15% of patients because of hepatocellular toxicity. Recent studies using human liver microsomes have suggested that a single liver enzyme, cytochrome P450 1A2 Tacrine (1,2,3,4-tetrahydro-9 acridinamine monohy-(CYP1A2), catalyzes the major route of metabolism and drochloride monohydrate; Cognex, Parke Davis Pharelimination of tacrine, and also catalyzes the pathway(s) maceuticals, Morris Plains, NJ), a potent acetylcholininvolved in the generation of reactive metabolites capa-esterase inhibitor, is the first therapeutic agent shown ble of covalent protein binding and cytotoxicity. Because to have significant benefit in the treatment of cognitive CYP1A2 activity has been shown to vary up to 60-fold deficits in patients with Alzheimer's disease. [1][2][3][4][5] It has among patients, we proposed that a convenient measure been estimated that approximately 3 to 4 million sured CYP3A4 and CYP2D6 activities also failed to predict the susceptible patients. However, the result of the However, susceptibility to tacrine liver toxicity clearly standardized-dose CBT correlated well with the loga-varies greatly in the Alzheimer's population, and at rithm of the steady-state plasma tacrine level obtained least two patients receiving tacrine have developed in 10 patients (R 2 Å .69, P Å .003). We conclude that the clinical jaundice indicative of severe hepatocellular in-CBT will not be clinically useful in determining the sub-jury. 8,9 A liver biopsy obtained in one of these patients set of patients most susceptible to tacrine hepatotoxic-revealed massive centrilobular necrosis. 8 In light of the ity. However, the correlation we observed between the potential risk for serious liver injury and the fact that CBT results and tacrine blood levels is the first evidence patients with serum transaminase elevations are gen-

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Section: Methodsmentioning

confidence: 99%

The Caffeine Breath Test Does Not Identify Patients Susceptible to Tacrine Hepatotoxicity

et al. 1996

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“…After collection of a blank urine sample, dextromethorphan (30 mg) was administered orally to a subset of these subjects, as previously described ( 18). Urine was collected over the next 4 h, aliquots frozen, and later thawed and assayed by high performance liquid chromatography for dextromethorphan and its polymorphically formed metabolite, dextrorphan ( 19). The molar concentration ratio of dextromethorphan/dextrorphan was used to assign phenotype, which has been previously shown to exactly co-segregate with that assigned using debrisoquin itself ( 19).…”

Section: Methodsmentioning

confidence: 99%

“…Urine was collected over the next 4 h, aliquots frozen, and later thawed and assayed by high performance liquid chromatography for dextromethorphan and its polymorphically formed metabolite, dextrorphan ( 19). The molar concentration ratio of dextromethorphan/dextrorphan was used to assign phenotype, which has been previously shown to exactly co-segregate with that assigned using debrisoquin itself ( 19). A urinary metabolic ratio < 0.3 defined extensive metabolizers (EMs) and values 2 0.3 defined subjects with the CYP2D6 deficiency (PMs), consistent with the antimode previously established by population studies of blacks and whites in our laboratory (3) and by others (20).…”

Section: Methodsmentioning

confidence: 99%

Genetic basis for a lower prevalence of deficient CYP2D6 oxidative drug metabolism phenotypes in black Americans.

Evans¹,

Relling²,

Rahman³

et al. 1993

J. Clin. Invest.

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Debrisoquin hydroxylase (CYP2D6) is a cytochrome P450 enzyme that catalyzes the metabolism of > 30 commonly prescribed medications. Deficiency in CYP2D6 activity, inherited as an autosomal recessive trait, was found to be significantly less common in American blacks (1.9%) than whites (7.7%). To determine the genetic basis for this difference, inactivating CYP2D6 mutations were assessed by allele-specific PCR amplification and RFLP analyses of genomic DNA from 126 unrelated whites and 127 unrelated blacks. Blacks had a twofold lower frequency (8.5 versus 23%, P = < 0.001) of the CYP2D6(B) mutation (point mutation at intron 3/exon 4 splice site), while complete deletion of the CYP2D6 gene (5.5% blacks, 2.4% whites), and the CYP2D6(A) mutation (single nucleotide deletion in exon 5; 0.24% blacks, 1.4% whites) were not different between the two groups. The prevalence of heterozygous genotypes was significantly lower in blacks (25 versus 42% of extensive metabolizers, P = 0.009), consistent with the observed prevalence of the deficient trait in blacks and whites. We conclude that the same CYP2D6 mutations lead to a loss of functional expression in blacks and whites, but American blacks have a lower prevalence of the deficient trait due to a lower frequency of the CYP2D6(B) mutation. This could explain racial differences in drug effects and disease risk. (J. Clin. Invest. 1993. 91:2150-2154

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“…In this study, the choice of chloroform/isopropanol as the extracting solvent resulted in some improved recovery of DMP compared to previous reports [14,19]. The analytical method employed in this study is one of the few methods that can detect DMP and its metabolite DP.…”

Section: Discussionmentioning

confidence: 83%

“…Various methods have been described in literature for the determination of DMP and DP in urine, which include high-performance liquid chromatography (HPLC) with fluorescence detection [9-13], HPLC with ultraviolet detection [14], and gas chromatography with flame ionization [15], and mass spectrometric detection [16]. Specific quantitation was obtained in most of these methods but assay sensitivity was inadequate for the determination of the metabolites.…”

Section: Introductionmentioning

confidence: 99%

Sensitive and Selective Reversed-Phase High Performance Liquid Chromatographic-UV Spectrophotometric Determination of Dextromethorphan and its CYP2D6 Mediated Metabolite, Dextrorphan in Human Urine

Ebeshi¹,

Obodozie²,

Bolaji³

2014

Trop. J. Pharm Res

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Quantitative Determination of Dextromethorphan and Three Metabolites in Urine by Reverse-Phase High-Performance Liquid Chromatography

Cited by 79 publications

References 6 publications

The Caffeine Breath Test Does Not Identify Patients Susceptible to Tacrine Hepatotoxicity

The Caffeine Breath Test Does Not Identify Patients Susceptible to Tacrine Hepatotoxicity

Genetic basis for a lower prevalence of deficient CYP2D6 oxidative drug metabolism phenotypes in black Americans.

Sensitive and Selective Reversed-Phase High Performance Liquid Chromatographic-UV Spectrophotometric Determination of Dextromethorphan and its CYP2D6 Mediated Metabolite, Dextrorphan in Human Urine

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