Pharmacokinetics of Camonagrel in experimental animal: rat, rabbit and dog.
Camonagrel is a novel selective thromboxane synthetase inhibitor. The aim of this study was to determine its main pharmacokinetic parameters in rats, rabbits and dogs after intravenous and oral administration at doses of 10 mg kg(-1). Plasma and urine concentrations of camonagrel were analyzed by HPLC with UV detection. Pharmacokinetics of camonagrel was generally fitted to a two-compartmental model and the values which defined the absorption process were: Cmax = 15.96 microg.ml(-1), Tmax approximately 0.33 h, AUC(0-infinity) (oral) approximately 12.45 microg x h x ml(-1) (rat, n=3 per pont); Cmax approximately 2.04 mg x ml(-1), Tmax approximately 1.50 h, AUC(0-infinity) (oral) approximately 4.85 microg x h x ml(-1) (rabbit, n=3); Cmax approximately 18.60 microg x ml(-1), Tmax approximately 0.44 h, AUC(0-infinity) (oral) approximately 13.40 microg x h x ml(-1) (dog, n=4). The more representative values in the distribution and elimination phase were: protein binding rate approximately 80% in the three species ("in vitro" experiment); t(1/2beta) approximately 0.22 h (rat, i.v.), = 0.28 h (rabbit i.v.) and approximately 0.45 h (dog i.v.); CI approximately 635.73 ml x h(-1) (rat i.v.), approximately 448.26 ml x h(-1) (rabbit i.v.) and approximately 463.8 ml x h(-1) (dog i.v.). The absolute bioavailability of camonagrel was approximately 79.1% in rat, approximately 21.7% in rabbit and approximately 59.3% in dog. Available elimination data in rat indicated that Camonagrel was mainly excreted in urine (approximately 80%) as unchanged drug. An unknown minor metabolite (approximately 10%) was observed only after oral dosing. Finally, the main pharmacokinetic parameters of camonagrel in rats, rabbits and dogs are presented, which allow to define its absorption, distribution and elimination processes in these species.
Albet
C
C
Centro de Investigacion Grupo Ferrer, Barcelona, Spain.
Pérez
A
A
Rozman
E
E
Sacristan
A
A
Ortiz
J A
JA
D000042:Absorption; D000284:Administration, Oral; D000818:Animals; D004285:Dogs; D005260:Female; D005343:Fibrinolytic Agents / Q000493:pharmacokinetics* / Q000652:urine; D007189:Indans / Q000493:pharmacokinetics* / Q000652:urine; D007275:Injections, Intravenous; D008297:Male; D008657:Metabolic Clearance Rate; D011817:Rabbits; D051381:Rats; D013045:Species Specificity
D005343:Fibrinolytic Agents; D007189:Indans; C103583:camonagrel