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Exploration of the metabolism of dihydrocodeine via determination of its metabolites in human urine using micellar electrokinetic capillary chromatography
Institution:1. Department of Clinical Pharmacology, University of Bern, Murtenstrasse 35, CH-3010 Bern, Switzerland;2. Mundipharma Pharmaceutical Company, St. Alban-Vorstadt 91, CH-4006 Basel, Switzerland;1. Programa de Doctorado en Ciencias Biológicas y de la Salud, Universidad Autónoma Metropolitana, Unidad-Iztapalapa, Ciudad de México, México;2. Unidad de Investigación Médica en Enfermedades Neurológicas, Hospital de Especialidades, Centro Médico Nacional Siglo XXI, Instituto Mexicano del Seguro Social, Ciudad de México, México;3. Servicio de Neurología, Hospital de Pediatría, Centro Médico Nacional Siglo XXI, Instituto Mexicano del Seguro Social, Ciudad de México, México;4. Departamento de Ciencias Farmacéuticas de la Facultad de Química. Universidad de la República, Montevideo, Uruguay;5. Instituto Nacional de Salud Pública, Cuernavaca, México;1. Department of Chemistry, Faculty of Basic Sciences, Azarbaijan Shahid Madani University, Tabriz, 53714-161, Iran;2. Department of Chemistry, University of Ilam, Ilam, 69315-516, Iran;1. Genetics Unit, Children Hospital, Mansoura University, Mansoura, Egypt;2. Department of Chemistry, Biochemistry Division, Faculty of Science, Damietta University, New Damietta, Egypt;3. Department of Pediatrics, Faculty of Medicine, Mansoura University, Mansoura, Egypt;4. Clinical Genetics Department, National Research Centre, Cairo, Egypt;5. Biochemistry and Molecular Genetics Unit, Department of Basic Sciences, Faculty of Physical Therapy, Horus University – Egypt, New Damietta, Egypt;1. Graduate School of Engineering, Kyoto University, C-1 Katsura, Nishikyo-ku, Kyoto, Kyoto, 615-8540, Japan;2. Kanagawa Prefectural Enterprise Bureau, 1 Nihon-Odori, Naka-ku, Yokohama, Kanagawa, 231-8588, Japan;3. Aichi Public Enterprise Bureau, 3-1-2 Sannomaru, Naka-ku, Nagoya, Aichi, 460-8501, Japan;4. Waterworks Bureau, City of Kawasaki, 1 Miyamoto-cho, Kawasaki-ku, Kawasaki, Kanagawa, 210-8577, Japan;5. National Institute of Public Health, 2-3-6 Minami, Wako, Saitama, 351-0197, Japan;1. School of Environment, Harbin Institute of Technology, Harbin 150090, PR China;2. National Engineering Center of Urban Water Resources, 202 Hehai Road, Harbin 150090, PR China;3. Evides Industriewater B.V. Schaardijk 150, Rotterdam 3063 NH, the Netherlands
Abstract:After single-dose administration of 40 or 60 mg of dihydrocodeine (DHC, in a slow-release tablet) to four healthy individuals known to be extensive metabolizers of debrisoquine, the urinary excretion of DHC and its four major metabolites, dihydrocodeine-6-glucuronide, nordihydrocodeine, dihydromorphine and nordihydromorphine, was assessed using micellar electrokinetic capillary chromatography (MECC). DHC and two of its metabolites (dihydrocodeine-6-glucuronide and nordihydrocodeine) could be analyzed by direct urine injection, whereas the metabolic pattern was obtained by copolymeric bonded-phase extraction of the solutes from both plain and hydrolyzed urine specimens prior to analysis. The total DHC equivalents exceted within 8 and 24 h were determined to be 30.4 ± 7.7% (n = 5) and 63.8 ± 6.1% (n = 2), respectively, and only about 4% of the excreted DHC equivalents were identified as morphinoids. Furthermore, almost no morphinoid metabolites of DHC could be found after administration of quinidine (200 mg of quinidine sulfate) 2 h prior to DHC intake.
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