Disposition of a new nonsteroidal anti-inflammatory agent, S-2-[4-(3-methyl-2-thienyl)phenyl]propionic acid, in rats, dogs and monkeys.
The disposition of S-2-[4-(3-methyl-2-thienyl)phenyl]propionic acid (CAS 155680-07-2, S-MTPPA, code: M-5011) was studied after oral administration to rats, dogs and monkeys using the 14C-labeled drug. After oral dosing, S-MTPPA was well absorbed from the gastrointestinal tract, to the extent of 97.7% in rats. The concentration of S-MTPPA in rat plasma reached a peak (Cmax: 13.07 micrograms/ml) at 15 min (tmax) after dosing and declined with a half-life (t1/2) of 2.5 h. The values of the parameters tmax, Cmax and t1/2 for dogs were 30 min, 26.2 micrograms/ml and 7.0 h, and those for monkeys were 15 min, 12.8 micrograms/ml and 3.0 h, respectively. The radioactivity was widely distributed in tissues and almost completely excreted in urine and feces within 48 h after oral administration to rats. The excretion of radioactivity in bile, urine and feces within 48 h after oral administration of 14C-S-MTPPA to bile duct-cannulated rats amounted to 75.0, 18.6 and 1.4% of the dose, respectively. The drug was metabolized mainly by oxidation of the thiophenyl moiety and by glucuronidation of the carboxyl group in rats and monkeys. The major urinary and fecal metabolite in dogs was identified as the taurine conjugate of MTPPA.
Konishi
T
T
Research and Development Laboratories, Maruho Co., Ltd., Osaka, Japan.
Okada
S
S
Nishikawa
H
H
Esumi
Y
Y
Kitamura
S
S
Tatsumi
K
K
D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000097:blood / Q000493:pharmacokinetics* / Q000652:urine; D019540:Area Under Curve; D004285:Dogs; D005243:Feces / Q000737:chemistry; D005260:Female; D006207:Half-Life; D008253:Macaca mulatta; D008297:Male; D010666:Phenylpropionates / Q000097:blood / Q000493:pharmacokinetics* / Q000652:urine; D051381:Rats; D017207:Rats, Sprague-Dawley; D013045:Species Specificity; D014018:Tissue Distribution
D000894:Anti-Inflammatory Agents, Non-Steroidal; D010666:Phenylpropionates; C104139:2-(4-(3-methyl-2-thienyl)phenyl)propionic acid