Carbon tetrachloride-induced pharmacokinetic changes of diazepam in rats are reduced by a stable analogue of prostaglandin E2 : FCE 20700.
Rats, given CC14 (6670 mg/Kg, sc), exhibited a significant increase in SGPT (425.7 +/- 51.3 mU/ml), together with impaired pharmacokinetics of intravenous diazepam (t beta 1/2: 53.87 h; AUC: 101.05 micrograms/ml/h) when compared with saline treated animal (SGPT: 33.6 +/- 3.8 mU/ml; t beta 1/2: 2.087 h; AUC: 1.37 micrograms/ml/h). FCE 20700 (5 micrograms/ml, sc) did not change, by itself, either SGPT or diazepam pharmacokinetic parameters, but significantly antagonized the changes induced by CC14 (SGPT: 45.3 +/- 5.3 mU/ml; t beta 1/2: 0.167 h; AUC: 2.426 micrograms/ml/h). Further support to this cytoprotective effects was given by histological examination of the livers. Data indicate that this new prostaglandin E2 derivative might be useful in patients with liver failure.
D000410:Alanine Transaminase / Q000097:blood; D000818:Animals; D002252:Carbon Tetrachloride Poisoning / Q000378:metabolism*; D056486:Chemical and Drug Induced Liver Injury / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control; D003451:Cryoprotective Agents / Q000494:pharmacology*; D003975:Diazepam / Q000378:metabolism*; D015232:Dinoprostone / Q000031:analogs & derivatives*; D005260:Female; D007700:Kinetics; D008099:Liver / Q000473:pathology; D011459:Prostaglandins E, Synthetic / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains
D003451:Cryoprotective Agents; D011459:Prostaglandins E, Synthetic; C040808:FCE 20700; D000410:Alanine Transaminase; D015232:Dinoprostone; D003975:Diazepam