INFLUENCE OF A NEWLY DEVELOPED QUINOLONE, T-3761, ON PHARMACOKINETICSOF THEOPHYLLINE IN RATS

The effect of a new quinolone, T-3761, on the pharmacokinetics and met abolism of theophylline was investigated with rats. T-3761 at a high d ose (20 mg/kg of body weight) was injected intravenously 10 min before an intravenous administration of theophylline (10 mg/kg). The presenc e of T-3761 slightly delayed the disappearance of theophylline from pl asma. Parameters related to the pharmacokinetic interaction between th eophylline and T-3761 were estimated by noncompartmental methods. A si gnificant decrease (approximately 25%) in the systemic clearance of th eophylline was observed in the presence of T-3761. However, no signifi cant changes between the control group and the T-3761-treated groups i n the volume of distribution at a steady state were observed. Pretreat ment with T-3761 increased the urinary excretion of unchanged theophyl line (by approximately 25%) and decreased the nonrenal clearances (by approximately 30%), indicating that T-3761 inhibits the metabolism of theophylline. These findings suggest that T-3761 at the dose used in t his study affects the pharmacokinetics and metabolism of theophylline.