Pharmacokinetics of coumarin and 7-hydroxycoumarin upon i.v. and p.o. administration in the euthyroid and hypothyroid beagle dog.
The pharmacokinetics of coumarin (C) and 7-hydroxycoumarin (7HC) ahs been studied after i.v. and p.o. administration in beagle dogs. C was given i.v. in doses of 0.25 and 0.5 mg/kg, respectively, and p.o. 1 mg/kg; 7HC was given i.v.in a dose size of 0.5 mg/kg and p.o. 1 mg/kg to euthyroid dogs. Upon administration of C the drug concentration-time profiles were determined for unchanged C and for 7HC after hydrolysis of the glucuronide. Upon administration of 7HC the concentration -time profiles were determined for unchanged 7HC and 7HC after hydrolysis of the glucuronide after i.v. dosing, and of 7HC after deglucuronidation after p.o. dosing. Additionally, the disposition of C upon i.v. administration was studied in hypothyroid beagles. Statistical analysis was performed on the data for the slow disposition rate constant, biological half-life, volume of distribution, total clearance, fraction of drug metabolized and rate of metabolism. Significant differences were found between euthyroid and hypothyroid dogs for both C and 7HC. The pharmacokinetics of C and 7HC in the dog is much different from that in man.
D000284:Administration, Oral; D000818:Animals; D003374:Coumarins / Q000008:administration & dosage / Q000378:metabolism*; D004285:Dogs; D007037:Hypothyroidism / Q000378:metabolism*; D007275:Injections, Intravenous; D007700:Kinetics; D008297:Male; D014468:Umbelliferones / Q000008:administration & dosage / Q000378:metabolism*
D003374:Coumarins; D014468:Umbelliferones