Phase I study of quinotolast sodium. Single-dose and multiple-dose studies

The safety and pharmacokinetics of quinotolast sodium, a new anti-allergic drug, were examined in healthy male volunteers in a single- or multiple-dose study. In the single-dose study, 10 subjects were given an oral dose of 10, 20, 40 or 80 mg of quinotolast sodium in a fasting state. In the multiple-dose study, 8 subjects were divided into two groups of 6 subjects for quinotolast treatment and 2 for placebo treatment. The subjects from active or placebo group were given, in a single blind manner, an oral dose of 40 mg of quinotolast sodium or placebo twice a day in the morning and evening (q 12 h) for seven days and once in the morning on day 8. Quinotolast sodium was well tolerated by all subjects. Clinically significant adverse effects were not observed in the single- and multiple-dose studies. In the single-dose study, plasma concentrations of quinotolast peaked 2.4 hours after dosing, and declined biexponentially with a terminal half-life of 9.9 hours. The maximum plasma concentration and area under the plasma concentration-time curve increased in proportion to the dose. In the multiple-dose study, plasma concentrations reached steady state by day 5. Quinotolast was hardly excreted unchanged in the urine.