Pharmacokinetics of radiolabelled quinlukast in rats

• Published in: Journal of pharmaceutical and biomedical analysis 2005-06, Vol.38 (2), p.313-319
• Main Authors: Syrovatko, Matej, Laznickova, Alice, Laznicek, Milan
• Format: Article
• Language: English
• Subjects: Analysis; Analytical, structural and metabolic biochemistry; Animals; Bile - metabolism; Biological and medical sciences; Chromatography, High Pressure Liquid - methods; Cyclic S-Oxides - blood; Cyclic S-Oxides - urine; Drug Evaluation, Preclinical - methods; Fundamental and applied biological sciences. Psychology; General pharmacology; Half-Life; HPLC; Injections, Intravenous; Liver - metabolism; Liver perfusion; Male; Medical sciences; Metabolic Clearance Rate; Perfusion; Pharmacokinetics; Pharmacology. Drug treatments; Quinlukast; Quinolines - administration & dosage; Quinolines - blood; Quinolines - pharmacokinetics; Radiopharmaceuticals - administration & dosage; Radiopharmaceuticals - pharmacokinetics; Rats; Rats, Wistar; Solubility; Tritium
• ISSN: 0731-7085; 1873-264X
• DOI: 10.1016/j.jpba.2005.01.011

Pharmacokinetics together with in vivo metabolism and elimination of quinlukast, a potential anti-asthmatic and anti-inflammatory drug, were designed in rats. For this purpose, bile duct cannulated rats and an in situ perfused rat liver preparation were employed. 3H-radiolabelled compound was administered i.v. or loaded to the perfusion medium, respectively. Quinlukast represented the main form of radioactivity determined in plasma; in comparison with the parent drug metabolites were present in lower levels in the systemic circulation. The pharmacokinetic parameters related to the whole animal were calculated from quinlukast rat plasma concentration–time course. The distribution of quinlukast in the body was relatively fast (distribution half-life was approx. 6 min), the elimination half-life exceeded 2 h. Binding of quinlukast to rat plasma proteins was very high (approx. 99.7%) and this binding influenced distribution volumes of quinlukast. Both the volume of the central compartment and the volume at a steady state were approx. 115 and 430 ml, respectively. The experiments showed that the biliary clearance was the major route of elimination of this compound from the systemic circulation of rats. In agreement with the determined elimination half-life approx. 42% of the radioactivity was found in the bile, with