Carbon tetrachloride-induced pharmacokinetic changes of diazepam in rats are reduced by a stable analogue of prostaglandin E2 : FCE 20700
Saija, A.; Padovano, I.; Puzzolo, D.; Ceserani, R.; Costa, G.
Research Communications in Chemical Pathology and Pharmacology 50(2): 221-232
1985
ISSN/ISBN: 0034-5164 PMID: 3841222 Document Number: 266366
Rats, given CCl4 (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 .mu.g/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 .mu.g/ml/h). FCE 20700 (5 .mu.g/ml, sc) did not change, by itself, either SGPT or diazepam pharmacokinetic parameters, but significantly antagonized the changes induced by CCl4 (SGPT: 45.3 .+-. 5.3 mU/ml; t.beta.1/2: 0.167 h; AUC: 2.426 .mu.g/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.