Summary
The metabolism of methaqualone to the glucuronides of 5 C-monohydroxy metabolites and to the N-oxide has been studied in 2 groups of healthy young adults phenotyped as extensive and poor metabolisers of debrisoquine. No significant interphenotype differences were observed with respect to the excretion of any of the 6 metabolites. It is probable that the genetic regulation of the pathways leading to these metabolites is at a locus other than that which is responsible for the regulation of the oxidation of debrisoquine, guanoxan, phenacetin, phenytoin and sparteine.
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References
Alván G, Lindgren J, Bogentoft G, Ericsson Ö (1973) Plasma kinetics of methaqualone in man after single oral doses. Eur J Clin Pharmacol 6:187–190
Burnett D, Reynolds CN, Wilson K, Francis JR (1976) Urinary excretion of C-hydroxy derivatives of methaqualone in man. Xenobiotica 6:125–134
Eichelbaum M, Spannbrucker N, Dingler HJ (1978) A probably genetic defect of the metabolism of sparteine. In: Gorrod JW (ed) Biological oxidation of nitrogen. Elsevier/North Holland, Amsterdam, pp 113–118
Eichelbaum M, Spannbrucker N, Steincke B, Dengler HJ (1979) Defective N-oxidation of sparteine in man: a new pharmacogenetic defect. Eur J Clin Pharmacol 16:183–187
Evans DAP, Mahgoub A, Sloan TP, Idle JR, Smith RL (1980) A family and population study of the genetic polymorphism of debrisoquine oxidation in the British white population. J Med Genet 17:102–105
Gorrod J (1978) The current status of the pKa concept on the differentiation of enzymic N-oxidation. In: Gorrod JW (ed) Biological oxidation of nitrogen, Elsevier/North Holland, Amsterdam, pp 201–210
Idle JR, Oates NS, Shah RR, Smith RL (1981) Is there a genetic predisposition to phenformin-induced lactic acidosis? Br J Clin Pharmacol 11:418–419
Inaba T, Otton SV, Kalow W (1980) Deficient metabolism of debrisoquine and sparteine. Clin Pharmacol Ther 27:547–549
Irvine RE, Grove J, Toseland PA, Trounce JR (1974) The effect of age on the hydroxylation of amylobarbitone sodium in man. Br J Clin Pharmacol 1:41–43
Mahgoub A, Idle JR, Dring LG, Lancaster R, Smith RL (1977) The polymorphic hydroxylation of debrisoquine in man. Lancet 2:584–586
Manowitz P, Shull CM (1976) Methaqualone metabolism by rat liver microsomes. Res Comm Chem Pathol Pharmacol 13:27–39
McReynolds JH, Heck H, Anabar M (1975) Determination of picomole quantities of methaqualone and 6-hydroxymethaqualone in urine. Biomed Mass Spectrom 2:299–303
Reynolds CN, Wilson K, Burnett D (1976) Urinary excretion of methaqualone-N-oxide in man. Xenobiotica 6:113–124
Reynolds CN, Wilson K, Burnett D (1978) Metabolism of methaqualone in geriatric patients. Eur J Clin Pharmacol 13:285–290
Sloan TP, Mahgoub A, Lancaster R, Idle JR, Smith RL (1978) Polymorphism of carbon oxidation and clinical implications. Br Med J 2:655–657
Sloan TP, Idle JR, Smith RL (1981) Influence of DH/DL alleles regulating debrisoquine oxidation on phenytoin hydroxylation. Clin Pharmacol Ther 29:493–497
Smyth RD, Lee JK, Polk A, Chemburkar PB, Savacool AM (1973) Bioavailability of methaqualone. J Clin Pharmacol 13:391–400
Wakile LA, Sloan TP, Idle JR, Smith RL (1979) Genetic evidence for the involvement of different oxidative mechanisms in drug oxidation. J Pharm Pharmacol 31:350–354
Wilson K, Reynolds CN, Burnett D (1978) Inter- and intra-individual variation in the metabolism of methaqualone in man after a single oral dose. Eur J Clin Pharmacol 13:291–297
Ziegler DM (1980) Microsomal flavin-containing monoxygenase: oxygenation of nucleophilic nitrogen and sulphur compounds. In: Jakoby WB (ed) Enzymic basis of detoxication. Academic Press, New York, pp 201–227
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Oram, M., Wilson, K., Burnett, D. et al. Metabolic oxidation of methaqualone in extensive and poor metabolisers of debrisoquine. Eur J Clin Pharmacol 23, 147–150 (1982). https://doi.org/10.1007/BF00545969
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DOI: https://doi.org/10.1007/BF00545969