Search results for "Permeability"
showing 10 items of 596 documents
Improvement of trospium-specific absorption models for fasted and fed states in humans
2014
The purpose of this study was to mechanistically interpret the oral absorption pattern of trospium in fasted and fed states by means of gastrointestinal simulation technology. A drug absorption model was built on the basis of experimental data. According to the generated model, low permeability across the intestinal epithelium, delayed gastric emptying time and a prolonged residence time in the small intestine are the key factors governing trospium absorption in the fasted state. Furthermore, in silico modelling provided a plausible explanation of the pronounced reduction in the oral bioavailability of trospium when administered with food. The simulation results support the decreased dissol…
Variability of permeability estimation from different protocols of subculture and transport experiments in cell monolayers.
2014
Abstract Introduction In vitro models with high predictive ability have been revealed as strong tools for pharmaceutical industry. However, the variability in permeability estimations complicates the comparison and combination of data from different laboratories and it makes necessary the careful validation of the model and the continuous suitability demonstration. The adequate standardization of pre-experimental, experimental and post-experimental factors might help to reduce the inter- and intra-laboratory variability in permeability values. Methods The objective of this paper is the evaluation of the effect of passage number, experimental protocol, time after seeding and calculation meth…
Biopartitioning micellar chromatography to predict skin permeability
2003
Dermal absorption of chemicals is an area of increasing interest to the pharmaceutical and cosmetic industries, as well as in dermal exposure and risk assessment processes. In this paper the capability of biopartitioning micellar chromatography (BMC) as an in vitro technique to describe compound percutaneous absorption is evaluated. A multivariate study (principal component analysis, partial least squares) is performed in order to evaluate the importance of some physicochemical variables on the skin permeability constant values. From these results, a quantitative retention-activity relationship model for predicting the skin permeability constants that uses the BMC retention data and melting…
Roflumilast inhibits leukocyte-endothelial cell interactions, expression of adhesion molecules and microvascular permeability
2007
Background and purpose: The present study addressed the effects of the investigational PDE4 inhibitor roflumilast on leukocyte-endothelial cell interactions and endothelial permeability in vivo and in vitro. Experimental approach: In vivo, intravital video-microscopy was used to determine effects of roflumilast p.o. on leukocyte-endothelial cell interactions and microvascular permeability in rat mesenteric venules. In vitro, the effects of roflumilast N-oxide, the active metabolite of roflumilast in humans, and other PDE4 inhibitors on neutrophil adhesion to tumour necrosis factor α (TNFα)-activated human umbilical vein endothelial cells (HUVEC), E-selectin expression and thrombin-induced e…
Muscarinic acetylcholine receptor trafficking in streptolysin O-permeabilized MDCK cells.
1996
We investigated the validity of streptolysin O (SLO)-permeabilized Madin-Darbin canine kidney (MDCK) cells which express muscarinic acetylcholine receptors (mAChRs) coupled to pertussis toxin-sensitive guanine nucleotide-binding proteins (G proteins) for the study of the molecular machinery that regulated mAChR internalization and recycling. Exposure of SLO-permeabilized cells to carbachol-reduced cell surface receptor number by up to 40% without changing total receptor number. The kinetics and maximal extent of receptor internalization as well as the potency of carbachol to induce receptor internalization were almost identical in SLO-permeabilized and non-permeabilized cells. Using this se…
Influence of Rhein on Rat Colonic Na<sup>+</sup>, K<sup>+</sup>-ATPase and Permeability in vitro
1988
Rhein, an aglucone of a laxative-acting anthraquinone, which induces net secretion in the human jejunum and colon, does not induce net secretion under open circuit current in in vitro conditions but r
Über die Wirkung von Prostaglandin E1 auf den Ca-Haushalt isolierter Meerschweinchenherzen
1967
The stimulatory effect of PGE1 on different functions of isolated guinea-pig hearts (Langendorff method, Tyrode solution) was coupled with an increase in the rate of45Ca uptake from the perfusion medium. The total myocardial Ca content and the amount of exchangeable cellular Ca were not affected. This action of PGE1 on the myocardial Ca metabolism seems to be related to the positive inotropic action of PGE1 and can most probably be explained by an increase in the membrane permeability to Ca ions (similar to the action of epinephrine).
�ber den Mechanismus der positiv inotropen Wirkung von Theophyllin am Warmbl�terherzen
1971
In order to further elucidate the mechanism of the positive inotropiceffect of theophylline (T) in mammalian cardiac muscle, the influence of T on contractile force, extracellular space,45Ca uptake,45Ca release, and total myocardial calcium concentration was investigated in isolated, electrically driven (frequency 170 beats/min) or quiescent left guinea-pig atria. The investigations were performed in Tyrode solution containing 0.45 mM CaCl2. T concentration was 5×10−4 g/ml. Under these conditions, T exerted maximal positive inotropic but no toxic effects, that is, it did not cause contractures or arrythmias within 60 min (Fig. 1). The experiments provide evidence that T increases the rate o…
Co-administration of pentoxifylline and thiopental causes death by acute pulmonary oedema in rats
2006
Background and purpose: Pentoxifylline exhibits rheological properties that improve microvascular flow and it is widely used in vascular perfusion disorders. It also exhibits marked anti-inflammatory properties by inhibiting tumour necrosis factor a production. Thiopental is one of the most widely used drugs for rapid induction of anaesthesia. During experimental studies on the treatment of acute pancreatitis, we observed that when pentoxifylline was administered after anaesthesia with thiopental, most of the rats exhibited dyspnea, signs of pulmonary oedema and died. The aim of the work described here was to investigate the cause of the unexpected toxic effect of the combined treatment wit…
Der Einflu� von Monojodessigs�ure auf das Aktionspotential des Rattenzwerchfells
1959
1. The action of iodoacetic acid (IA) was studied on the isolated rat diaphragm at 20–22° C. Membrane and action potentials were led off with intracellular microelectrodes. 2. IA causes a contracture which is complete in 4 hours. As long as t he contracture develops, the membrane potential remains constant. A contracture identical with that seen in a normal preparation can be produced by IA in the presence of isotonic K2SO4. 3. The amplitude of the action potential is only slightly reduced during the first two hours after addition of IA. The duration of the action potential is significantly increased. Finally, action potentials with a plateau are obtained which resemble those of normal vent…