Correlations among the metabolic ratios of three test probes (metoprolol, debrisoquine and sparteine) for genetically determined oxidation polymorphism in a Japanese population. 1990

Y Horai, and J Taga, and T Ishizaki, and K Ishikawa
Division of Clinical Pharmacology, Nihon University School of Medicine, Tokyo, Japan.

The study was aimed at defining the relationships among the oxidative capacities for three prototype drugs, metoprolol, debrisoquine and sparteine, used for assessing genetically determined polymorphism of drug oxidation in a Japanese population. Among 292 unrelated healthy Japanese subjects who had been defined as extensive (EMs, n = 291) or poor (PM, n = 1) metabolisers of metoprolol oxidation, 55 subjects (EMs = 54 and PM = 1) were selected. One PM of metoprolol oxidation was also identified as a PM not only of debrisoquine but also of sparteine, and no misclassification by the three phenotypic methods was observed. All three correlations among the metabolic ratios of the three test probes assessed by Spearman's rank test were highly significant (P less than 0.001). These findings indicate that in Japanese subjects the oxidation capacities of metoprolol, debrisoquine, and sparteine are closely related. It appears that in Japanese the polymorphic oxidation of the three drugs is co-regulated, either by the same enzyme or gene-controlling system.

UI MeSH Term Description Entries
D007546 Isoquinolines A group of compounds with the heterocyclic ring structure of benzo(c)pyridine. The ring structure is characteristic of the group of opium alkaloids such as papaverine. (From Stedman, 25th ed)
D007564 Japan A country in eastern Asia, island chain between the North Pacific Ocean and the Sea of Japan, east of the Korean Peninsula. The capital is Tokyo. Bonin Islands
D008297 Male Males
D008790 Metoprolol A selective adrenergic beta-1 blocking agent that is commonly used to treat ANGINA PECTORIS; HYPERTENSION; and CARDIAC ARRHYTHMIAS. Beloc-Duriles,Betaloc,Betaloc-Astra,Betalok,CGP-2175,H 93-26,Lopressor,Metoprolol CR-XL,Metoprolol Succinate,Metoprolol Tartrate,Seloken,Spesicor,Spesikor,Toprol,Toprol-XL,Beloc Duriles,Betaloc Astra,CGP 2175,CGP2175,H 93 26,H 9326,Metoprolol CR XL,Toprol XL
D008875 Middle Aged An adult aged 45 - 64 years. Middle Age
D010084 Oxidation-Reduction A chemical reaction in which an electron is transferred from one molecule to another. The electron-donating molecule is the reducing agent or reductant; the electron-accepting molecule is the oxidizing agent or oxidant. Reducing and oxidizing agents function as conjugate reductant-oxidant pairs or redox pairs (Lehninger, Principles of Biochemistry, 1982, p471). Redox,Oxidation Reduction
D011110 Polymorphism, Genetic The regular and simultaneous occurrence in a single interbreeding population of two or more discontinuous genotypes. The concept includes differences in genotypes ranging in size from a single nucleotide site (POLYMORPHISM, SINGLE NUCLEOTIDE) to large nucleotide sequences visible at a chromosomal level. Gene Polymorphism,Genetic Polymorphism,Polymorphism (Genetics),Genetic Polymorphisms,Gene Polymorphisms,Polymorphism, Gene,Polymorphisms (Genetics),Polymorphisms, Gene,Polymorphisms, Genetic
D003647 Debrisoquin An adrenergic neuron-blocking drug similar in effects to GUANETHIDINE. It is also noteworthy in being a substrate for a polymorphic cytochrome P-450 enzyme. Persons with certain isoforms of this enzyme are unable to properly metabolize this and many other clinically important drugs. They are commonly referred to as having a debrisoquin 4-hydroxylase polymorphism. Debrisoquine,Tendor
D005260 Female Females
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man

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