A realistic ex vivo model, the isolated perfused rat lung (IPRL), was used to investigate tobramycin's pulmonary disposition at typical therapeutic concentrations. Different nominal doses were administered in aqueous solution to the airways alongside nonbinding absorption markers, fluorescein and mannitol. The mean fraction of each administered dose reaching the perfusate (Fp) was determined as...

Trichloroacetic acid (TCA) is a contaminant of drinking water. It induces peroxisome proliferation in livers of rats and mice and is hepatocarcinogenic in the latter species. Previous experimental studies of the kinetics of TCA in the isolated perfused rat liver (IPRL) at two doses have been reported. To gain more insight into the mechanistic processes controlling TCA kinetics in the liver a bi...

the isolated perfused rat liver (iprl) model has been used into toxicology study of rat liver. this model provides an opportunity at evaluation of liver function in an isolated setting. studies showed that cd, in a dose-dependent manner, induced toxic effects in iprl models, and these effects were associated with aminotransferase activity and lipid peroxidation. the aim of this study was to inv...

Penclomedine is a multi-chlorinated alpha-picoline derivative that has demonstrated activity in several murine breast cancer models and is currently in clinical testing for use against solid tumors. This study evaluates the metabolism of penclomedine in several in vitro hepatic models, including microsomes, fresh liver slices, and the isolated perfused rat liver (IPRL). Both human and mouse liv...

For many years, the isolated perfused rat liver (IPRL) model has been used to investigate the physiology and pathophysiology of the rat liver. This in vitro model provides the opportunity to assess cellular injury and liver function in an isolated setting. This review offers an update of recent developments regarding the IPRL set-up as well as the viability parameters that are used, with regard...

Atorvastatin (ATV) is primarily metabolized by CYP3A in the liver to form two active hydroxy metabolites. Therefore, the sequential transport system governed by hepatic uptake and efflux transporters is important for the drug disposition and metabolism. Here, we assessed the interaction of ATV with hepatic uptake transporter organic anion transporting polypeptide (Oatp) and efflux transporter m...

4-(Methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) is a lung-specific tobacco carcinogen. Metabolism is critical to its elimination given its lipophilic nature. Although NNK can be metabolized through detoxification pathways that safely eliminate it from the body, it can also be bioactivated, resulting in the formation of potentially carcinogenic DNA adducts. The isolated perfused rat lung (I...

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 ...

BACKGROUND The isolated perfused rat liver (IPRL) is a technique used in a wide range of liver studies. Typically livers are assessed at treatment end point. Techniques have been described to biopsy liver in the live rat and post-hepatectomy. RESULTS This paper describes a technique for obtaining two full and one partial lobe biopsies from the liver in situ during an IPRL experiment. Our appr...

The organic cation transporters OCT and OCTN have been reported to play a significant role in the cellular uptake of substrates within in vitro lung cells. However, no studies to date have investigated the effect of these transporters upon transepithelial absorption of substrates into the pulmonary circulation. We investigated the contribution of OCT and OCTN transporters to total pulmonary abs...