Search results for "Intestinal permeability"
showing 10 items of 40 documents
Segmental-dependent permeability throughout the small intestine following oral drug administration: Single-pass vs. Doluisio approach to in-situ rat …
2016
Abstract Intestinal drug permeability is position dependent and pertains to a specific point along the intestinal membrane, and the resulted segmental-dependent permeability phenomenon has been recognized as a critical factor in the overall absorption of drug following oral administration. The aim of this research was to compare segmental-dependent permeability data obtained from two different rat intestinal perfusion approaches: the single-pass intestinal perfusion (SPIP) model and the closed-loop (Doluisio) rat perfusion method. The rat intestinal permeability of 12 model drugs with different permeability characteristics (low, moderate, and high, as well as passively and actively absorbed…
The effects of three absorption-modifying critical excipients on the in vivo intestinal absorption of six model compounds in rats and dogs.
2018
Pharmaceutical excipients that may affect gastrointestinal (GI) drug absorption are called critical pharmaceutical excipients, or absorption-modifying excipients (AMEs) if they act by altering the integrity of the intestinal epithelial cell membrane. Some of these excipients increase intestinal permeability, and subsequently the absorption and bioavailability of the drug. This could have implications for both the assessment of bioequivalence and the efficacy of the absorption-enhancing drug delivery system. The absorption-enhancing effects of AMEs with different mechanisms (chitosan, sodium caprate, sodium dodecyl sulfate (SDS)) have previously been evaluated in the rat single-pass intestin…
Use of nonlinear mixed effect modeling for the intestinal absorption data: application to ritonavir in the rat.
2005
The aim of this study is to investigate in situ the mechanisms involved in the gastrointestinal absorption of ritonavir in the rat, as an animal model for preclinical studies of anti-HIV agents in vivo. Four ritonavir solutions (40, 27, 13 and 7 microM) in the presence of 1% dimethylsulfoxide (DMSO) were perfused in the small intestine of anaesthetised rats. Effects of DMSO on the intestinal permeability were investigated using solutions containing antipyrine 1.33 mM and ritonavir 7 microM with and without 1% of DMSO. Antipyrine and ritonavir transport was not modified in the presence of 1% of DMSO. The population pharmacokinetic parameters of the ritonavir intestinal transport were obtaine…
Intestinal transport of cefuroxime axetil in rats: absorption and hydrolysis processes.
2002
Studies were performed using three cefuroxime axetil solutions (11.8, 118 and 200 microM) in three selected intestinal segments and one cefuroxime axetil solution (118 microM) in colon of anaesthetized rats. First-order absorption rate pseudoconstants, k(ap) and effective permeability coefficients, P(eff), were calculated in each set. Absorption of cefuroxime axetil can apparently be described as a carrier-mediated transport, which obeys Michaelis-Menten and first order kinetics in the proximal segment of the small intestine and a passive diffusion mechanism in the mean and distal segments. The absorption kinetic parameters for cefuroxime axetil were obtained: Vm=0.613 (0.440) microM min-1;…
Comparison of segmental-dependent permeability in human and in situ perfusion model in rat.
2017
Abstract Nowadays, alternative methods have been developed to predict intestinal permeability values in human as in vitro, in situ or ex vivo methods. They were developed by the necessity to avoid the problems of the human permeability experiments. However, determination of human permeability is needed to properly validate the alternative methods. For this reason, recently, Dahlgren et al. published an indirect method based on a deconvolution technique to estimate the human permeability in different gastrointestinal segments (jejunum, ileum and colon). Therefore, the objective of this research was to demonstrate that Doluisio technique is a useful method to predict the human permeability in…
Prevention of Rat Intestinal Injury with a Drug Combination of Melatonin and Misoprostol
2020
A healthy intestinal barrier prevents uptake of allergens and toxins, whereas intestinal permeability increases following chemotherapy and in many gastrointestinal and systemic diseases and disorders. Currently, there are no approved drugs that target and repair the intestinal epithelial barrier while there is a medical need for such treatment in gastrointestinal and related conditions. The objective of this single-pass intestinal perfusion study in rats was to investigate the preventive cytoprotective effect of three mucosal protective drugs&mdash
Endotoxaemia resulting from decreased serotonin tranporter (5-HTT) function: A reciprocal risk factor for depression and insulin resistance?
2015
International audience; Depression and diabetes are serious diseases with an increasing global prevalence. Intriguingly, recent meta-analyses have highlighted an asymmetrical relationship between the two conditions as depressed patients were found to display a higher risk of developing type 2 diabetes than those individuals suffering from diabetes are to become depressed. Based on recent findings, we favor a hypothesis where by decreased peripheral serotonin (5-HT) transporter (5-HTT) function is a reciprocal risk factor for the comorbidity of depression and diabetes, as it can trigger inflammatory pathogenetic mechanisms of both conditions. Higher intestinal levels of 5-HT and 5-HT3 recept…
The effect of chitosan on the bioaccessibility and intestinal permeability of acyclovir
2019
Chitosan is object of pharmaceutical research as a candidate permeability enhancer. However, chitosan was recently shown to reduce the oral bioavailability of acyclovir in humans. The effect of chitosan on two processes determining the oral bioavailability of acyclovir, bioaccessibility and intestinal absorption, was now investigated. Acyclovir's bioaccessibility was studied using the dynamic TNO gastro-Intestinal Model (TIM-1). Four epithelial models were used for permeability experiments: a Caco-2 cell model in absence and presence of mucus and both rat and porcine excised intestinal segments. Study concentrations of acyclovir (0.8 g/l) and chitosan (1.6 g/l and 4 g/l) were in line with t…
Lipodepsipeptides from Pseudomonas syringae are partially proteolyzed and are not absorbed by humans: An in vitro study
2008
There are some concerns about the use of Pseudomonas-based products as biocontrol agents because of the hemolytic activity shown by their metabolites. The effects of Pseudomonas lipodepsipeptides (LDPs) on mammals via ingestion and the LDP degradation during the digestion and intestinal permeability have not been evaluated. In this research, the susceptibility of different LDPs to degradation was assayed with enzymatic gastrointestinal digestion, and intestinal permeability to LDPs was investigated in an in vitro system based on an intestinal cell layer system. Results demonstrated that trypsin and chymotrypsin hydrolyze up to 50% of the various LDPs, and that proteolysis was further increa…