SYUIQ-5, a novel telomerase inhibitor, has demonstrated antitumor activity in nude mouse studies. The objective of the present study was to examine the metabolism and pharmacokinetics of SYUIQ-5 in rats. The plasma pharmacokinetics of SYUIQ-5 was nonlinear following i.p. administration at 15, 30 and 60 mg/kg. SYUIQ-5 metabolism in rat liver microsomes followed Michaelis-Menten kinetics, with Km and Vmax values of 12.3 microM and 2.01 nmol/min/mg protein, respectively. Ketoconazole significantly inhibited the metabolism of SYUIQ-5 in liver microsomes from rats pretreated with control vehicle or various inducers, whereas sulphaphenazole, ticlopidine, quinidine, and methylpyrazole had no inhibitory effects on SYUIQ-5 metabolism. Dexamethasone and beta-naphthoflavone (BNF), but not phenobarbital and ethanol, significantly induced SYUIQ-5 metabolism in rats. Alpha-naphthoflavone significantly inhibited SYUIQ-5 metabolism in liver microsomes from BNF-pretreated rats. Similar to other secondary amines, SYUIQ-5 underwent N-demethylation and O-oxygenation to at least two metabolites by rat liver microsomes. Pretreatment of rats with SYUIQ-5 at 0.1, 5 or 10 mg/kg for 5 days significantly induced the expression and activity of rat Cyp1A1/2, and induced Cyp3A1/2 expression at 10 mg/kg, but not Cyp2E1 and 2B1/2. These results indicate that that SYUIQ-5 exhibits dose-dependent pharmacokinetics in rats and it is mainly metabolized by Cyp3A1/2.