Pharmacokinetics of the new antiplatelet agent 2-methyl-3-(1,4,5,6-tetrahydronicotinoyl)pyrazolo[1,5-a]pyridine in laboratory animals.
KC-764 (2-methyl-3-(1,4,5,6-tetrahydronicotinoyl)pyrazolo [1,5-a]pyridine CAS 94457-09-7) and its metabolites in serum and urine were determined after intravenous and oral administration in mice, rats, rabbits and dogs at a dose of 5 mg/kg. KC-764 was rapidly eliminated from serum in all species. The biological half-lives of unchanged KC-764 after intravenous administration in mice, rats, rabbits and dogs were 1.31, 0.29, 1.94 and 1.20 h, respectively. 2-Methyl-3-(1,4,5,6-tetrahydro-6-oxonicotinoyl)pyrazolo-[1,5-a]pyr idine was a common major metabolite in serum of all species, although 6,7-dihydro-6,7-dihydroxy-2-methyl-3-(1,4,5,6- tetrahydro-6-oxonicotinoyl) pyrazolo-[1,5-a]pyridine (M-8) was more abundant in rabbits. Urinary recovery of unchanged KC-764 was as low as 0.4-2.2% in all species. The major urinary metabolite was 2-methyl-3-(1,4,5,6-tetrahydro-6-ureidonicotinoyl)pyrazolo-[1,5-a] pyridine in mice, rats and dogs, but M-8 was in rabbits. KC-764 was rapidly and well absorbed by oral administration, and extensively metabolized in all species tested.
Komuro
M
M
Central Research Laboratories, Kyorin Pharmaceutical Co., Ltd., Tochigi, Japan.
Hori
W
W
Hotta
M
M
Saitoh
S
S
Ishida
R
R
Uchida
H
H
D000284:Administration, Oral; D000818:Animals; D001643:Bridged Bicyclo Compounds / Q000008:administration & dosage / Q000493:pharmacokinetics* / Q000652:urine; D004285:Dogs; D006207:Half-Life; D007275:Injections, Intravenous; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D009539:Nicotinic Acids / Q000008:administration & dosage / Q000493:pharmacokinetics* / Q000652:urine; D010975:Platelet Aggregation Inhibitors / Q000008:administration & dosage / Q000493:pharmacokinetics* / Q000652:urine; D011817:Rabbits; D051381:Rats; D011919:Rats, Inbred Strains
D001643:Bridged Bicyclo Compounds; D009539:Nicotinic Acids; D010975:Platelet Aggregation Inhibitors; C074536:KC 764