[Consumer study on the use of patient information leaflets].

The aim of this study was to get a clear idea of the reading frequency of the patient information leaflet (PIL) and to set up a profile of the reader in specific. Apart from that, we also wanted to evaluate the impact of the internet in the patient's search for information on health and medication. Do patients consult the digital PIL and is the FAGG website known by common people? In order to answer these research questions, a specific inquiry was performed in 800 respondents.

Characterization of fasted-state human intestinal fluids collected from duodenum and jejunum.

The solubility of drugs in the gastrointestinal tract is very challenging to simulate with artificial media due to the high complexity of human intestinal fluid (HIF). In particular, bile salt composition, pH and buffer capacity are very important characteristics of HIF, since they determine the solubility of drugs in-vivo. In this study, we have measured the concentrations of individual bile salts in human intestinal fluids (n=6) collected from two different locations (duodenum and jejunum) in the fasted state.

Sulfasalazine transport in in-vitro, ex-vivo and in-vivo absorption models: contribution of efflux carriers and their modulation by co-administration of synthetic nature-identical fruit extracts.

Sulfasalazine is characterised by low oral bioavailability. In this study, its intestinal transport characteristics were studied in an in-vitro, ex-vivo and in-situ system. The absorptive transport of sulfasalazine across Caco-2 monolayers appeared to be lower than the secretory transport (P(app-abs) = 0.

P-glycoprotein attenuating effect of human intestinal fluid.

Purpose: To evaluate the effect of human intestinal fluid (HIF) on P-glycoprotein (P-gp)-mediated efflux.

Methods: HIF was obtained from eight healthy volunteers by duodenal aspiration. HIF was applied at different concentrations (0-75%) to the apical compartment of the Caco-2 system.

Screening of Tanzanian plant extracts for their potential inhibitory effect on P-glycoprotein mediated efflux.

For years, many efforts have been made to discover new drugs using plants as natural screening libraries. In this study, extracts of 43 Tanzanian medicinal plants were screened for their potential inhibitory effect on P-gp, using the secretory transport of Cyclosporin A (CsA) in the Caco-2 system as a measure of the functionality of P-gp efflux. Two out of these 43 plant extracts (extracts of Annickia kummeriae and Acacia nilotica) appeared to have a modulatory effect on P-gp related efflux carriers.

The effect of food components on the absorption of P-gp substrates: a review.

P-glycoprotein (P-gp), a well characterized efflux mechanism which is functionally expressed in the intestinal epithelium, constitutes, along with intestinal metabolism, an important part of the biochemical barrier function of the intestinal mucosa. This efflux carrier may be responsible for limiting the bioavailability of several drugs after oral intake. Recently, increasing attention is being paid to the interaction of dietary components with the intestinal absorption of drugs.

Implementation of the caco-2 cell culture model as a predictive tool for the oral absorption of drugs. In-house evaluation procedures.

The Caco-2 cell culture model is widely used during drug development and lead optimization as a predictive tool for the oral absorption of drugs. In order to improve the reliability and quality of the results of Caco-2 experiments and to ensure that the system being used is functionally and enzymatically representative for the intestinal mucosa, it is important to perform a validation of the implemented Caco-2 system. In this paper, we summarize evaluation techniques to guarantee the in-house validity of the model.

Apricot extract inhibits the P-gp-mediated efflux of talinolol.

Within the framework of developing strategies to enhance the intestinal absorption of P-glycoprotein (P-gp) substrates, the modulatory effect of a standardized apricot extract on P-gp-related efflux carriers was investigated in the Caco-2 system, Ussing chambers and the rat in situ perfusion model using talinolol as a model substrate. Using the Caco-2 system, polarity in transport of talinolol could be observed, the absorptive transport being much lower than the secretory transport (P(app-abs) = 1.08 +/- 0.

Inhibitory effect of fruit extracts on P-glycoprotein-related efflux carriers: an in-vitro screening.

In this study, standardized food extracts were screened for their possible inhibitory effect on the P-glycoprotein (P-gp)-mediated efflux of 3H-ciclosporin A (CsA) using the in-vitro Caco-2 model. CsA is commonly used as a substrate for P-gp-related efflux carriers and is characterized by a polarity in transport, the absorptive transport being much lowerthan the secretorytransport (polarityfactor: PF approximately 7). Of the 68 tested, nine extracts showed a decreased efflux of CsA (< 75% of the reference value) and were retained for further experiments on the bidirectional transport of CsA across Caco-2 monolayers.

Intestinal absorption enhancement of the ester prodrug tenofovir disoproxil fumarate through modulation of the biochemical barrier by defined ester mixtures.

The effect of discrete esters and ester mixtures on the intestinal stability and absorption of tenofovir disoproxil fumarate (tenofovir DF, an esterase-sensitive prodrug of the antiviral tenofovir) was compared with the effect of strawberry extract, which has been shown to enhance the absorption of the prodrug across Caco-2 monolayers and in rat ileum. In addition, the mechanism of absorption enhancement was investigated. In rat intestinal homogenates, complete inhibition of the conversion of tenofovir DF (as obtained by strawberry extract) could only be obtained at relatively high concentrations of the discrete esters or by using mixtures of esters (e.

Intestinal absorption characteristics of the low solubility thiocarboxanilide UC-781.

The aim of this study was to determine the intestinal absorption characteristics of the antiviral agent UC-781 and to optimize the experimental conditions of the in vitro system for low solubility compounds. The absorption potential of UC-781 was studied with the Caco-2 system and with the rat intestinal perfusion technique. The low solubility of UC-781 required the use of solubility/dissolution rate enhancing agents (e.

Simulated intestinal fluid as transport medium in the Caco-2 cell culture model.

The Caco-2 model is widely used as a predictive tool for the oral absorption of drug candidates. Presently, transport experiments in the Caco-2 system are usually performed in 'HBSS-like' buffers. In this paper, we investigate the possibility of using simulated intestinal buffers as donor solvent during Caco-2 experiments.

New bis(SATE) prodrug of AZT 5'-monophosphate: in vitro anti-HIV activity, stability, and potential oral absorption.

The in vitro anti-HIV activity, stability, and potential for oral absorption of a phosphotriester derivative of AZT (zidovudine; 3'-azido-2',3'-deoxythymidine) bearing a new esterase-labile S-acyl-2-thioethyl (SATE) group as transient phosphate protection are reported. The biolabile protection is characterized by the presence of a hydroxyl function in the acyl chain. In accordance with previously reported data in the bis(SATE) prodrug series, the present results demonstrate that the studied bis(hydroxytBuSATE)phosphotriester exerts its biological effects via intracellular delivery of the 5'-monophosphate of AZT.

Increased absorption of the antiviral ester prodrug tenofovir disoproxil in rat ileum by inhibiting its intestinal metabolism.

Previous studies have shown that strawberry extract increases the transepithelial transport of tenofovir disoproxil, an esterase-sensitive prodrug of the antiviral compound tenofovir (formerly PMPA), across Caco-2 monolayers. This increase in transport was at least partially due to inhibition of its intestinal metabolism. To further study the feasibility of this absorption enhancing strategy, the influence of various concentrations of strawberry extract (0-2%) on the intestinal absorption of tenofovir disoproxil (100 microM) was assessed using an in situ perfusion model with immediate blood sampling from the mesenteric vein, a model closer to the in vivo situation than the in vitro Caco-2 system.