Abstract
The relationship between debrisoquine oxidation phenotype and the stereoselective metabolism of metoprolol was investigated in populations of British Caucasians (n = 139) and Nigerian subjects (n = 117). The 0-8 h urinary S/R-metoprolol (S/R-M) ratio was related to the ability to metabolise metoprolol and debrisoquine in both ethnic groups. The median S/R-M ratio was significantly higher in Caucasians (1.27) than in Nigerians (1.10). In the Caucasian population poor metabolisers of debrisoquine had significantly lower S/R-M ratio (median = 0.84) than extensive metabolisers (median = 1.28). Bimodality in the frequency distribution of the S/R-M ratio was not apparent in either ethnic group.
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- Iyun A. O., Lennard M. S., Tucker G. T., Woods H. F. Metoprolol and debrisoquin metabolism in Nigerians: lack of evidence for polymorphic oxidation. Clin Pharmacol Ther. 1986 Oct;40(4):387–394. doi: 10.1038/clpt.1986.195. [DOI] [PubMed] [Google Scholar]
- Lennard M. S. Quantitative analysis of metoprolol and three of its metabolites in urine and liver microsomes by high-performance liquid chromatography. J Chromatogr. 1985 Jul 12;342(1):199–205. doi: 10.1016/s0378-4347(00)84504-1. [DOI] [PubMed] [Google Scholar]
- Lennard M. S., Silas J. H., Smith A. J., Tucker G. T. Determination of debrisoquine and its 4-hydroxy metabolite in biological fluids by gas chromatography with flame-ionization and nitrogen-selective detection. J Chromatogr. 1977 Mar 11;133(1):161–166. doi: 10.1016/s0021-9673(00)89216-x. [DOI] [PubMed] [Google Scholar]
- Lennard M. S., Tucker G. T., Silas J. H., Freestone S., Ramsay L. E., Woods H. F. Differential stereoselective metabolism of metoprolol in extensive and poor debrisoquin metabolizers. Clin Pharmacol Ther. 1983 Dec;34(6):732–737. doi: 10.1038/clpt.1983.242. [DOI] [PubMed] [Google Scholar]
- McGourty J. C., Silas J. H., Lennard M. S., Tucker G. T., Woods H. F. Metoprolol metabolism and debrisoquine oxidation polymorphism--population and family studies. Br J Clin Pharmacol. 1985 Dec;20(6):555–566. doi: 10.1111/j.1365-2125.1985.tb05112.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Nakamura K., Goto F., Ray W. A., McAllister C. B., Jacqz E., Wilkinson G. R., Branch R. A. Interethnic differences in genetic polymorphism of debrisoquin and mephenytoin hydroxylation between Japanese and Caucasian populations. Clin Pharmacol Ther. 1985 Oct;38(4):402–408. doi: 10.1038/clpt.1985.194. [DOI] [PubMed] [Google Scholar]
- Wedlund P. J., Aslanian W. S., Jacqz E., McAllister C. B., Branch R. A., Wilkinson G. R. Phenotypic differences in mephenytoin pharmacokinetics in normal subjects. J Pharmacol Exp Ther. 1985 Sep;234(3):662–669. [PubMed] [Google Scholar]
- Wedlund P. J., Aslanian W. S., McAllister C. B., Wilkinson G. R., Branch R. A. Mephenytoin hydroxylation deficiency in Caucasians: frequency of a new oxidative drug metabolism polymorphism. Clin Pharmacol Ther. 1984 Dec;36(6):773–780. doi: 10.1038/clpt.1984.256. [DOI] [PubMed] [Google Scholar]