The influence of cimetidine on debrisoquine 4-hydroxylation in extensive metabolizers
We have studied the effect of cimetidine (800 mg·day−1) administration for three days on debrisoquine 4-hydroxylation in nine healthy extensive metabolizers.
The debrisoquine metabolic ratio was significantly increased (p<0.01), but the new ratios remained in the extensive metabolizer range (<12.6).
These data suggest that pre-treatment with cimetidine in usual therapeutic doses will impair debrisoquine 4-hydroxylation, but not enough to alter the apparent oxidation phenotype.
Key wordscimetidine debrisoquine drug interactions extensive metabolizers
Unable to display preview. Download preview PDF.
- Amsterdam JD, Brunswick DJ, Potter L, Kaplan MJ (1984) Cimetidine-induced alterations in desipramine plasma concentrations. Psychopharmacology 83: 373–375Google Scholar
- Bertilsson L, Aberg-Wistedt A (1983) The debrisoquine hydroxylation test predicts steady-state plasma levels of desipramine. Br J Clin Pharmacol 15: 388–389Google Scholar
- Clark DWG (1985) Genetically determined variability in acetylation and oxidation. Therapeutic implications. Drugs 29: 342–375Google Scholar
- Eichelbaum M (1982) Defective oxidation of drugs: Pharmacokinetic and therapeutic implications. Clin Pharmacokinet 7: 1–22Google Scholar
- Evans DAP, Mahgoub A, Sloan TP, Idle JR, Smith RL (1980) A family and population study of the genetic polymorphism of debrisoquine oxidation in a white British population. J Med Genet 17: 102–105Google Scholar
- Feely J, Wilkinson GR, Wood AJJ (1981) Reduction of liver blood flow and propranolol metabolism by cimetidine. N Engl J Med 304: 692–695Google Scholar
- Henauer SA, Hollister LE (1984) Cimetidine interaction with imipramine and nortriptyline. Clin Pharmacol Ther 35: 183–187Google Scholar
- Lennard MS, Silas JH, Smith AJ, Tucker GT (1977) Determination of debrisoquine and its 4-hydroxy metabolite in biological fluids by gas chromatography with flame-ionization and nitrogen-selective detection. J Chromatogr 133: 161–166Google Scholar
- Mahgoub A, Idle JR, Dring LG, Lancaster R, Smith RL (1977) Polymorphic hydroxylation of debrisoquine in man. Lancet 2: 584–586Google Scholar
- Sloan TP, Lancaster R, Shah RR, Idle JR, Smith RL (1983) Genetically determined oxidation capacity and the disposition of debrisoquine. Br J Clin Pharmacol 15: 443–450Google Scholar
- Somogyi A, Muirhead M (1987) Pharmacokinetic interactions of cimetidine. Clin Pharmacokinet 12: 321–366Google Scholar
- Somogyi A, Stockley C, Keal J, Rolan P, Bochner F (1987) Reduction of metformin renal excretion by cimetidine in man. Br J Clin Pharmacol 23: 545–551Google Scholar
- Steiner E, Iselius L, Alvan G, Lindsten J, Sjöqvist F (1985) A family study of genetic and environmental factors determining polymorphic hydroxylation of debrisoquine. Clin Pharmacol Ther 38: 394–401Google Scholar
- Von-Bahr C, Birgersson C, Morgan ET, Eriksson O, Goransson M, Spina E, Woodhouse K (1986) Oxidation of tricyclic antidepressant drugs, debrisoquine and 7-ethoxyresorufin, by human liver preparations. Xenobiotica 16: 391–400Google Scholar