Pharmacokinetics of quinotolast sodium in rats, guinea pigs and dogs

Abstract

The pharmacokinetics of quinotolas t sodium in rats, guinea pigs and dogs were studied after a single intravenous or oral dosing.
1. After intravenous dosing of 1mg/kg to rats, guinea pigs and dogs, the plasma concentration of quinotolast declined with respective terminal halflives of 1.8, 6.1, 10.4hr.
2. Total body clearance was 27.9, 6.8, 0.94ml/min/kg and the volume of distribution at steady state was 320, 1393 and 624ml, /kg in rats, guinea pigs and dogs respectively.
3. After oral dosing of 0.32 ?? 3.2mg/kg to rats, 1mg/kg to guinea pigs and 0.32 ?? 3.2mg/kg to dogs, the time to reach maximum plasma concentration was 5 ?? 20min, 2hr, 0.7 ?? 1.7hr and bioavailability was 0.55 ?? 0.64, 0.63, 0.55 ?? 0.85 respectively.
4. After oral dosing, the area under the plasma concentration-time curves in rats and dogs apeared to be proportional to dose over the range of 0.32 ?? 3.2mg/kg.
5. After oral dosing to rats, the area under the plasma concentration-time curves of quinotolast and hydroxy quinotolast were about the same, and it is considered that approximately 60% of quinotolast was metabolized to hydroxy quinotolast.