Debrisoquine metabolism

Turgeon J et al. Debrisoquine metabolic ratio (DMR) distribution differs among smokers and non-smokers. Am Soc Clin Pharmacol Ther 1995 PI61 150. 

Wennerholm A, Johansson I, Massele AY, Jande M, Alm C, Aden-Abdi Y et al. Decreased capacity for debrisoquine metabolism among black Tanzanians analyses of the CYP2D6 genotype and phenotype. Pharmacogenetics 1999 9 707-714. 

Yue, Q.Y., Aim, C., Svensson, J.O., Sawe, J. Quantification of the O- and N-demethylated and the glucuronidated metabolites of codeine relative to the debrisoquine metabolic ratio in urine in ultrarapid, rapid, and poor debrisoquine hydroxylators, Ther. Drug Monit. 1997, 19, 539-542. 

The deficiency of debrisoquine metabolism (19) was also tested in our laboratory, and we found a different metabolic ratio between Chinese and Caucasian students (34). These observations, together with the old G6PD and NAT2 data and some additional comparisons, firmly planted in my mind the idea that differences in drug metabolism are not only a matter of individuals but frequently occur also between the human populations. I published a review article that probably was the first exclusively concerned with interethnic differences of drug metabolism (35). Knowledge of such differences has become very important for the pharmaceutical industry. 

Figure 2 Frequency distributions of debrisoquine metabolic ratios (MR) in four populations. An alignment of data from four separate studies. The abscissa indicates on a logarithmic scale the metabolic ratio debrisoquine/4-OH-debrisoquine in urine after administration of a test dose of debrisoquine these are conventional plots in which the increasing ratios reflect decreasing metabolism. The black bars indicate subjects classified as genetically poor metabolizers, usually defined as subjects with a metabolic ratio >12.6. Each of the four inserts represents an adaptation of a published illustration so that their abscissas are comparable and aligned for MR of unity. The insert marked China represents a study of 269 Han, Africa a study of 92 Venda, Sweden a study of 752 Swedes, and Spain a study of 377 Spaniards. The entry for Africa is marked with an asterisk because it represents tribal data of unknown generality. The measurements from China and Sweden were comparable, as ensured by controls. Source Compiled from Refs. 1, 99-101.

Iyun AO, Lennard MS, Tucker GT, et al. Metoprolol and debrisoquin metabolism in Nigerians lack of evidence for polymorphic oxidation. Clin Pharmacol Ther 1986 40 387-394. 

LLerena A, Berecz R, de la Rubia A, Dorado P. QTC interval lengthening and debrisoquine metabolic ratio in psychiatric patients treated with oral haloperidol monotherapy. Eur J Clin Pharmacol 2002 58(3) 223 1. 

FIGURE 13.4 Distribution of the urinary debrisoquine/4-hydro)9 debrisoquine metabolic ratio (MR) in 695 Cliinese and 1011 Swedish healthy individuals. The arrows indicate MR = 12.6, the antimode between EMs and PMs established in Caucasians. A line is drawn at MR = 1. Most Chinese EMs have MR > 1, while most Swedish EMs have MR < 1. (Reproduced with permission from Bertilsson L et al. Clin Pharmacol Ther 1992 52 388-97.)... 

Gonzalez FJ, Skoda RC, Kimura S, Umeno M, Zanger UM, Nebert DW et al. Characterization of the common genetic defect in humans deficient in debrisoquine metabolism. Nature 1988 331 442-6. 

Gustafsson LL, Eriksson LS, Dahl ML, Eleborg L, Ericzon BG, Nyberg A. Cyclophosphamide-induced acute liver failure requiring transplantation in a patient with genetically deficient debrisoquine metabolism a causal relationship J. Intern Med 1996 240(5) 311-14. 

Figure 43-6 Histogram of the debrisoquine metabolic ratio in a typical Caucasian population. Metabolic ratios were determined from the concentrations of debrisoquine and 4-hydroxydebrisoquine (metabolite) in a urine specimen collected 8 hours after a 10 mg dose of debrisoquine.The data demonstrate a clear distinction between PM, EM, and UM phenotypes. (From Caldwell J. Pharmacogenetics and Individual variation in the range of amino acid adequacy the biological aspects. J Nutr 2004 134 16005 45 discussion 30S-32S, 67S-72S. Reproduced by permission from the American Society for Nutritional Sciences.)...

Debrisoquine metabolism in parkinsonian patients treated with antihistamine drugs. Lancet ii 386. 

E. J. Whibley, J.R. Idle, J. Ritchie et al. (1983). The genetic control of sparteine and debrisoquine metabolism in man with new methods of analysing bimodal distributions.,/ Med. Genet. 20, 321-329. 

Caporaso, N., R.B. Hayes, M. Dosemeci, R. Hoover, R. Ayesh, M. Hetzel et al. (1989). Lung cancer risk, occupational exposure, and the debrisoquine metabolic phenotype. Cancer Res. 49, 3675-3679. 

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, 34, 732-737. 

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