Re-evaluation of the metabolism of carbocisteine in a British white population
| Autor: | C O Meese, I Turner, O.F.W. James, W. L. Gregory, Jeffrey R. Idle |
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| Rok vydání: | 1993 |
| Předmět: |
Drug
Adult Male medicine.medical_specialty Urinary system media_common.quotation_subject Metabolite Urine White People chemistry.chemical_compound Biotransformation Internal medicine Genetics medicine Genetic predisposition Humans General Pharmacology Toxicology and Pharmaceutics media_common Aged Aged 80 and over Polymorphism Genetic Carbocysteine Metabolism Middle Aged United Kingdom Endocrinology Phenotype chemistry Carbocisteine Female medicine.drug |
| Zdroj: | Scopus-Elsevier |
| ISSN: | 0960-314X |
| Popis: | It has been claimed that the amino acid derivative carbocisteine is predominantly metabolized by sulfoxidation and that this pathway exhibits a genetic polymorphism. Moreover, those subjects with a 'poor metabolizer' phenotype have been thought to have a genetic predisposition to developing certain diseases. We have confirmed the observations of others that this marker drug does not undergo significant S-oxidation. Furthermore, a novel urinary metabolite, S-(carboxymethylthio)-L-cysteine (CMTC) has recently been identified. To determine if a genetic polymorphism for this biotransformation pathway exists, metabolic ratios (% urinary excretion carbocisteine/% urinary excretion CMTC) for 120 healthy volunteers were assessed using high-performance thin-layer chromatography. Urinary excretion of the parent drug ranged from 6% of the dose administered to 56% (mean +/- SD, 23.4 +/- 0.8%). No cysteinyl sulfoxide metabolites were identified in the urine samples. The amount excreted as CMTC exhibited a 12-fold variation but only accounted for mean of 4.4% (1-12%) of the dose given. Two individuals initially had high metabolic ratios (> 30), however, on rechallenge both their MRs were less than 5. Therefore, carbocisteine is not an appropriate probe drug for sulfoxidation. The formation of the novel metabolite CMTC appears to exhibit polymorphism, although the considerable intra-subject variation for its formation does not allow assignment of a phenotype. |
| Databáze: | OpenAIRE |
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