imatinib metabolism and disposition in isolated rat perfused liver

Imatinib metabolism and disposition in isolated rat perfused liver

Imatinib is an orally administered tyrosine kinase inhibitor which inhibits the Bcr-Abl protein-tyrosine kinase with high selectivity. Imatinib is rapidly absorbed from the gut, after oral intake and has an almost absolute bioavailability of 98%. The metabolism of imatinib is mediated by the cytochrome P450 (CYP) isoenzymes in the liver and gut wall. CGP74588 is a major active metabolite of ima...

Xylitol metabolism in the isolated perfused rat liver.

1. Loading the isolated perfused liver from well-fed rats with xylitol (20mm) caused a depletion of adenine nucleotides and P(i) and an accumulation of alpha-glycerophosphate. The ATP content fell to 66% of the control value after 10min and to 32% after 80min. The ADP and AMP contents also fell. After 80min 63% of the total adenine nucleotides and 59% of the P(i) had been lost. 2. The alpha-gly...

Phthalate ester metabolism in the isolated, perfused rat liver system.

A series of experiments, performed at Johns Hopkins University, which led to our finding that plasticizers are extracted from poly-(vinyl chloride) (PVC) plastic by blood and biologic fluids will be described. The experiments began with the appearance of an unknown compound in the isolated perfused liver system. Livers were perfused with a mixture of synthetic plasma containing bovine serum alb...

study on hepatobiliary disposition of etoposide in an isolated perfused rat liver model (iprl)

The isolated perfused rat liver.

The disposition of mefloquine has been investigated in the isolated perfused rat liver (IPRL) preparation after the administration of [C]mefloquine HCI (3.8 mg, 4 1 Ci, quinoline ring labeled). Mefloquine underwent avid hepatic uptake within 10 min of dosing. Also at this point, hepatic oxygen consumption was reduced markedly in four of the six IPRL preparations, but was restored completely by ...

Disposition and covalent binding of diflunisal and diflunisal acyl glucuronide in the isolated perfused rat liver.

Acyl glucuronides are intrinsically reactive metabolites of carboxylate drugs, capable of undergoing hydrolysis, intramolecular rearrangement (isomerization via acyl migration), and intermolecular transacylation reactions. Transacylation with nucleophilic groups located on protein molecules leads to covalent drug-protein adducts. Protein adducts can also form from the rearrangement isomers via ...