Debrisoquine hydroxylation

Smeraldi, E., Zanardi, R. et al. (1998). Polymorphism within the promoter of the serotonin transporter gene and antidepressant efficacy of fluvoxamine. Mol. Psychiatry, 3(6), 508-11. Wang, S. L., Huang, J. D. et al. (1993). Molecular basis of genetic variation in debrisoquin hydroxylation in Chinese subjects polymorphism in RFLP and DNA sequence of CYP2D6. Clin. Pharmacol. Ther., 53(4), 410-18. 

Johansson, I., Oscarson, M., Yue, Q. Y. etal. (1994). Genetic analysis of the Chinese cytochrome P-4502D locus characterization of variant CYP2D6 gene present in subjects with diminished capacity for debrisoquine hydroxylation. Mol. Pharmacol. 46, 452-9. 

Llerena A, Edman G, Cobaleda J, Ben itez J, SchaUing D, et al. 1993. Relationship between personality and debrisoquine hydroxylation capacity. Suggestion of an endogenous neuroactive substrate or product of the cytochrome P4502D6. Acta Psychiatrica Scandinavica 87 23-28. 

Data from Woolhouse et al Debrisoquin hydroxylation polymorphism among Ghanians and Caucasians. Clin Pharmacol Ther 1979 26 584.)... 

As an example of the first type of chiral effect, metabolism of the drug bufuralol may be considered. Hydroxy la tion in the V position only occurs with the (+) isomer, whereas for hydroxylation in positions 4 and 6, the (—) isomer is the preferred substrate (Fig. 5.3). Glucuronidation of the side chain hydroxyl group is specific for the (+) isomer. A further complication in human subjects is that the 1-hydroxylation is under genetic control, being dependent on the debrisoquine hydroxylator status (see below). The selectivity for the isomers for the hydroxylations is virtually abolished in poor metabolizers. 

Lof, A., Hansen, S.H Naslund. P, Steiner, E., Wallen, M. Hjelm, E.W. (1990a) Relationship between uptake and elimination of toluene and debrisoquin hydroxylation polymorphism. Clin. Pharmacol. Ther., 47, 412 417... 

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. 

Q.Y. Yue, L. Bertilsson, M.L. Dahl-Puustinen, J. Sawe, F. Sjoqvist, I. Johansson, M. Ingelman-Sundberg, Dissociation between Debrisoquine Hydroxylation Phenotype and Genotype among Chinese , Lancet, ii, 870 (1989). 

Wang SL, Huang JD, Lai MD, Liu B-H, Lai M-L. Molecular basis of genetic variation in debrisoquine hydroxylation in Chinese subjects polymorphism in RFLP and DNA sequence of CYP2D6. Clin Pharmacol Ther 1993 53 410-418. 

Llerena A, Aim C, Dahl M-L, Ekqvist B, Bertilsson L. Haloperidol disposition is dependent of debrisoquine hydroxylation phenotype. Ther Drug Monit 1992 14 92-97. 

Gan SH, Ismail R, Wan Adnan WA, Zulmi W, Kumaraswamy N, Larmie ET. Relationship between types A and B personality and debrisoquine hydroxylation capacity. Br J Clin Pharmacol 2004 57 785-789. 

Bertilsson L, Aim C, De Las Carreras C, Widen J, Edman G, Schalling D. Debrisoquine hydroxylation polymorphism and personality. Lancet 1989 555. 

Lou YC, Ying L, Bertilsson L, Sjoqyist F. Low frequency of slow debrisoquine hydroxylation in a native Chinese population. Lancet 1987 2 852-853. 

Steiner E, Bertilsson L, Sawe J, Bertling I, Sjoqvist F. Polymorphic debrisoquine hydroxylation in 757 Swedish subjects. Clin Pharmacol Ther 1988 44 431-435. 

Oates NS, Shah RR, Idle JR, et al. Phenformin-induced lacticacidosis associated with impaired debrisoquine hydroxylation. Lancet 1981 l(8224) 837-838. 

Schmid B, Bircher J, Preisig R, et al. Polymorphic dextromethorphan metabolism co-segregation of oxidative O-demethylation with debrisoquine hydroxylation. Clin Pharmacol Ther 1985 38 618-624. 

Inaba T, Otton SV, Kalow W. Debrisoquine hydroxylation capacity problems of assessment in two populations. Clin Pharmacol Ther 1981 29 218-223. 

Lerena A, Valdivielso MJ, Benitez J, et al. Reproducibility over time of mephenytoin and debrisoquine hydroxylation phenotypes. Pharmacol Toxicol 1993 73 46 18. 

Bertilsson L, Eichelbaum M, Mellstrom B, Sawe J, Schulz H-U, Sjoqvist E. Nortryptyline and antipyrine clearance in relation to debrisoquine hydroxylation in man. Life Sci 1980 27 1673-7. 

Distlerath, L. M., Reilly, E E, B., Martin, M. V Wilkinson, G. R., and Guengerich, E E (1985). Immunochemical Characterization of the Human Liver Cytochrome P450 Involved in Debrisoquine Hydroxylation, In Microsomes and Drug Oxidations (A. R. Boobis, J. Caldwell, E De Matters, and C. R, Elcombe, eds.), Taylor Francis, London, pp. 380-389. 

Steiner E, Spina E. Differences in the inhibitory effect of cimetidine on desipramine metabolism between rapid and slow debrisoquin hydroxylators. Chn Pharmacol Ther 1987 42(3) 278-82. 

Lledo P, Abrams SM, Johnston A, Patel M, Pearson RM, Turner P. Influence of debrisoquine hydroxylation phenotype on the pharmacokinetics of mexiletine. Eur J Clin Pharmacol 1993 44(l) 63-7. 

Armstrong, M., Daly, A.K., Cholerton, S., Bateman, N. and Idle, J.R. (1992) Mutant debrisoquine hydroxylation genes in Parkinson s disease. Lancet 339 1017-1018. 

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