Abstract: Experimental animal models of hypothyroidism and hyperthyroidism were established in SD rats and the influence of different thyroid status on oxidative metabolism ofdiazepam was studied. After a single oral dose of diazepam 30-40 mg.kg^-1 to the rats, the plasmaconcentration of desmethyldiazcpam and temazepam which are two principle metabolites ofdiazepam was determined by HPLC method. The plasma concentration of desmethyldiazepam wassignificantly higher in hypothyroid rats than in control rats and the elimination was inhibited. Itshowed that hypothyroidism inhibited C3-hydroxylation of desmethyldiazepam but did not influenceN-demethylation of diazepam. The plasma concentration of temazepam was decreased inhyperthyroid rats. The plasma concentration of desmethyldiazepam was decreased and theelimination was accelerated in mild and moderate hyperthyroid rats. On the contrary, the plasmaconcentration of desmethyldiazepam was increased and the elimination was inhibited in severehyperthyroid rats. The results suggested that hyperthyroidism inhibited C3-hydroxylation of diazepam,but did not influence N-demethylation of diazepam. Mild and moderate hyperthyroidism accelerated C3-hydroxylation of desmethyldizepam, however, severe hyperthyroidism inhibited this metabolic pathway.

Key words: Different thyroid status, Hypothytoidism, Hyperthyroidism, Diazepam, Oxidative metabolism, Desmethyldiazepam, Temazepam