Drugs online research references
J Pharm Sci. 1990 Jun;79(6):476-82.
Epithelial transport of drugs in cell culture. I: A model for studying the passive diffusion of drugs over intestinal absorptive (Caco-2) cells.
Artursson P.
Department of Pharmaceutics, Uppsala University, Sweden.
A human intestinal cell line, Caco-2, was used as a model to study the passive diffusion of drugs across intestinal epithelium. The cells formed continuous monolayers when grown on permeable filters of polycarbonate. After 10 days in culture, the monolayers had a transmembrane resistance of approximately 260 ohms.cm2 and a cell density of 0.9 x 10(6) cells/cm2. At this time the cells were impermeable to [14C]polyethyleneglycol (MW 4000). These characteristics remained constant for 20 days (i.e., from day 10 to day 30). Six beta-blocking agents with a 2000-fold range of lipophilicity were studied for their transepithelial transport properties. The transport parameters were independent of drug concentration and transport direction. The apparent permeability coefficients ranged from 41.91 +/- 4.31 x 10(-6) cm/s for the most lipophilic drug, propranolol, to 0.203 +/- 0.004 x 10(-6) cm/s for the most hydrophilic drug, atenolol. The transport parameters were compared with those published for rat ileum. The transport rates were similar for four out of five drugs. Atenolol was transported at a slower rate in the Caco-2 model, which may be explained by the fact that the Caco-2 cells form a tighter epithelium than the rat ileal enterocytes. The findings of this paper indicate that Caco-2 cells may be used to model the intestinal absorption of drugs.
online pharmacy ref source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=1975619&dopt=Abstract
J Pharm Sci. 1990 Jul;79(7):595-600.
Epithelial transport of drugs in cell culture. II: Effect of extracellular calcium concentration on the paracellular transport of drugs of different lipophilicities across monolayers of intestinal epithelial (Caco-2) cells.
Artursson P, Magnusson C.
Department of Pharmaceutics, Uppsala University, Sweden.
A human intestinal cell line, Caco-2, was used as a model to study the passive diffusion of a homologous series of drugs (beta-blocking agents) of different lipophilicity across intestinal epithelium. The permeability of the Caco-2 monolayers was modulated by the use of a calcium switch assay. The transmembrane resistance could be reversibly decreased from approximately 280 ohms.cm2 (a resistance similar to that of colon epithelium) to approximately 60 ohms.cm2 (a resistance similar to that of small intestine epithelium). Transmission electron microscopy showed that the increased electrical permeability was caused by a reversible separation of the components of the junctional complex and not by cell detachment. In general, the increased paracellular permeability resulted in a 2- to 9-fold increase in the apparent permeability coefficients for the more hydrophilic drugs (e.g., from 0.20 +/- 0.010 x 10(-6) to 1.43 +/- 0.185 x 10(-6) cm/s for atenolol), while the transport parameters for the more lipophilic drugs remained unchanged (e.g., 43.03 +/- 3.64 x 10(-6) and 46.10 +/- 3.25 x 10(-6) cm/s for propranolol). These findings indicate that it is possible to study the contribution of the paracellular pathway to the transport of drugs in the Caco-2 model.
online pharmacy ref source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=2118955&dopt=Abstract
Horm Metab Res. 1990 Mar;22(3):188-91.
Effect of adrenergic agonists on human chorionic gonadotropin release by human trophoblast cells obtained from first trimester placenta.
Oike N, Iwashita M, Muraki T, Nomoto T, Takeda Y, Sakamoto S.
Department of Pharmacology, Tokyo Women's Medical College, Japan.
The cultured syncytiotrophoblast cells from human first trimester placenta were used to determine the effect of adrenergic agonists on human chorionic gonadotropin (hCG) production in vitro. Beta-adrenergic agonists isoproterenol, ritodrine and isoxsuprine increased the hCG release during the 2 h incubation period, however, alpha-agonists norepinephrine and phenylephrine and a beta 1-agonist dobutamine had no effect. The effect of isoproterenol was blocked by propranolol and butoxamine, but less efficiently by phentolamine and atenolol. These results indicate that placental hCG production can be modulated by stimulation of beta-, possibly beta 2-adrenoceptors but not by alpha-adrenoceptors.
online pharmacy ref source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=1971614&dopt=Abstract
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