Pharmacokinetics and hepatoprotective effects of 2-methylaminoethyl-4,4 '-dimethoxy-5,6,5 ',6 '-dimethylenedioxybiphenyl-2-carboxylic acid-2 '-carboxylate monohydrochloride in rats with CCl4-induced acute hepatic failure

Citation
Sy. Oh et al., Pharmacokinetics and hepatoprotective effects of 2-methylaminoethyl-4,4 '-dimethoxy-5,6,5 ',6 '-dimethylenedioxybiphenyl-2-carboxylic acid-2 '-carboxylate monohydrochloride in rats with CCl4-induced acute hepatic failure, J PHARM PHA, 52(9), 2000, pp. 1099-1103
Citations number
20
Language
INGLESE
art.tipo
Article
Categorie Soggetti
Pharmacology & Toxicology
Journal title
JOURNAL OF PHARMACY AND PHARMACOLOGY
ISSN journal
0022-3573 → ACNP
Volume
52
Issue
9
Year of publication
2000
Pages
1099 - 1103
Database
ISI
SICI code
0022-3573(200009)52:9<1099:PAHEO2>2.0.ZU;2-7
Abstract
The pharmacokinetics and hepatoprotective effects of 2-methylaminoethyl-4,4 '-dimethoxy-5,6,5', 6'-dimethylenedioxybiphenyl-2- carboxylic acid-2'-carbo xylate monohydrochloride (DDB-S) have been investigated in rats with CCl4-i nduced acute hepatic failure. To study the pharmacokinetics of DDB-S, rats were divided into a control gr oup and a CCl4-intoxicated group. DDB-S 50 mg kg(-1) was administered by in travenous bolus injection to both groups of rats. In the CCl4-intoxicated r ats the plasma concentrations of DDB-S were significantly higher, the area under the plasma concentration-time curve from time zero to time infinity w as significantly greater (6.46 vs 3.34 mg min mL(-1)), and the total body ( 7.74 vs 15.0 mL min(-1) kg(-1)), renal (2.55 vs 5.10 mL min(-1) kg(-1)), no nrenal (5.07 vs 9.65 mL min(-1) kg(-1)), and biliary (1.48 vs 2.69 mL min(- 1) kg(-1)) clearances were significantly slower compared with the control r ats. This could be due to decreased hepatic cytochrome P450 activity and im paired kidney function induced by CCl4. To study the hepatoprotective effects of DDB-S, rats were divided into thre e groups, control rats and CCl4-intoxicated rats with or without DDB-S pret reatment (50 mg kg(-1) i.p.). The effects of DDB-S pretreatment on CCl4-ind uced liver injury were considerable; the serum levels of alanine transamina se, aspartate transaminase, and alkaline phosphatase were significantly low er by 54.3, 44.6 and 67.2%, respectively, compared with the CCl4-intoxicate d-only group. In an in-vitro study, rat hepatocytes were exposed to fresh medium containi ng 10 mM CCl4 and various concentrations of DDB-S (10 or 100 mu g mL(-1)). The levels of alanine transaminase and aspartate transaminase in the medium were measured as an indicator of hepatocyte injury. DDB-S dose-dependently decreased the levels of alanine transaminase and aspartate transaminase co mpared with CCl4-intoxication only. These results indicate that DDB-S has hepatoprotective activity.