[The depression of hepatic drug-metabolizing enzyme activity in rats with carrageenan-induced inflammation. II. The effect on the status of plasma antipyrine concentration in rats].
The variation of hepatic drug-metabolism was investigated in male Wistar rats bearing hind paw edema induced by carrageenan (1%, 0.1 ml, s.c.). The content of cytochrome P-450 and the biotransformation of aminopyrine in the hepatic 9000 x g supernatant (S-9) decreased after the subcutaneous injection of carrageenan to rat hind paw. In carrageenan-treated rats the plasma concentration of antipyrine after the administration of antipyrine (20 mg/kg, i.v.) was higher than that of control rats. In comparison with the control groups, the pharmacokinetic parameters of antipyrine in carrageenan-treated rats was altered. AUC0-200 and t 1/2 significantly increased and CLtot and ke significantly decreased. On the other hand, no change of the volume of distribution (Vd) was observed. The results indicate that the hepatic drug metabolism under the carrageenan-induced inflammation is inhibited both in vitro and in vivo.
Sasaki
K
K
Cancer Research Institute, Tohoku College of Pharmacy, Sendai, Japan.
Ishikawa
M
M
Takayanagi
Y
Y
Sasaki
K
K
D000633:Aminopyrine N-Demethylase / Q000378:metabolism*; D000818:Animals; D000983:Antipyrine / Q000097:blood / Q000493:pharmacokinetics*; D002351:Carrageenan; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism*; D004487:Edema / Q000139:chemically induced / Q000201:enzymology / Q000378:metabolism*; D008658:Inactivation, Metabolic; D008297:Male; D051381:Rats; D011919:Rats, Inbred Strains
D002351:Carrageenan; D003577:Cytochrome P-450 Enzyme System; D000633:Aminopyrine N-Demethylase; D000983:Antipyrine