Pharmacokinetics of the new antiplatelet agent 2-methyl-3-(1,4,5,6-tetrahydronicotinoyl)pyrazolo[1,5-a]pyridine in human subjects.
The pharmacokinetics of KC-764 (2-methyl-3-(1,4,5,6-tetrahydronicotinoyl)pyrazolo[1,5-a]pyridine, CAS 94457-09-7) was studied in healthy male adult volunteers after single ascending oral dose and multiple dosing for 7 days. Serum KC-764 concentration attained the peak in 1 h and declined with a half-life of about 2 h at a single oral dose of 5, 10, 20 and 40 mg. No dose dependent pharmacokinetics of KC-764 was demonstrated. Three metabolites were detected in serum, but their concentrations were lower than that of KC-764. 48-h urinary recoveries after single doses were 41.6-46.6% of dose, not being dose-dependent. Urinary recovery of unchanged KC-764 was 1.1-1.6% of dose. Three metabolites were present in greater amount in urine than unchanged KC-764 and two metabolites were less than KC-764. There was little daily variation of serum concentrations and urinary excretion of KC-764 and its metabolites in the multiple dosing (20 mg twice a day) study. The daily and total urinary recovery were same as those after single doses. Food reduced Cmax and tended to delay tmax, but did not influence AUC0----infinity and urinary recovery. Serum protein binding of KC-764 was about 60%, being not dependent on total serum concentration.
Nakashima
M
M
Department of Pharmacology, Hamamatsu University School of Medicine, Shizuoka, Japan.
Kanamaru
M
M
Uematsu
T
T
Mizuno
A
A
Toriumi
C
C
Hotta
M
M
Komuro
M
M
Ishida
R
R
Uchida
H
H
D000328:Adult; D001643:Bridged Bicyclo Compounds / Q000097:blood / Q000493:pharmacokinetics* / Q000652:urine; D005502:Food; D006207:Half-Life; D006801:Humans; D008297:Male; D009539:Nicotinic Acids / Q000097:blood / Q000493:pharmacokinetics* / Q000652:urine; D010975:Platelet Aggregation Inhibitors / Q000097:blood / Q000493:pharmacokinetics* / Q000652:urine; D011485:Protein Binding
D001643:Bridged Bicyclo Compounds; D009539:Nicotinic Acids; D010975:Platelet Aggregation Inhibitors; C074536:KC 764