Drugs online research references
J Pharm Pharmacol. 2000 Feb;52(2):157-62.
Effects of some non-ionic surfactants on transepithelial permeability in Caco-2 cells.
Dimitrijevic D, Shaw AJ, Florence AT.
Centre for Drug Delivery Research, The School of Pharmacy, University of London, UK.
The effects of the non-ionic surfactants polysorbate 20, polysorbate 60, polysorbate 85, cholesteryl poly (24) oxyethylene ether (Solulan C24) and the lanolin-based poly (16) oxyethylene ether (Solulan 16) on the epithelial integrity of monolayers of human intestinal epithelial (Caco-2) cells has been studied using metformin as a model drug. The aim was to identify the surfactants and their optimal concentrations capable of enhancing drug transport while causing no, or only minor, cellular damage. Effects on cell permeability were assessed by measurements of the transport of metformin, a hydrophilic drug, by monitoring transepithelial electrical resistance. Cell viability was determined by the diphenyltetrazolium bromide test (the MTT test). All the surfactants studied demonstrated concentration-dependent effects on cell permeability and cell viability. The effects on transepithelial electrical resistance correlated with cell viability, i.e. increased transepithelial electrical resistance and increased cell-monolayer permeability for metformin corresponded to decreased cell viability. The results indicate that the Solulan and polysorbate surfactants were active as absorption enhancers, Solulan C24 and 16 being more effective than polysorbates 20, 60 or 85, causing an increase in metformin transport at lower concentrations than the polysorbates. Polysorbate 20 exerted its greatest effect at a concentration of 5%-increasing the flux of metformin after 3 h by a factor of around 20 over the control. Large increases in the transport of metformin, especially at surfactant levels of 0.05%, 0.1% and 0.5%, were related to the effect of Solulan C24 and Solulan 16 on the cell permeability. The Caco-2 cell monolayer experiments confirmed the ability, especially of polysorbate 20, Solulan C24 and Solulan 16, to increase the absorption of metformin. The polysorbates increased permeability as a result of solubilisation of membrane components, while Solulans did so by penetrating and solubilising the membrane. Correlation between increase in membrane permeability and the toxicity of the surfactants towards the cell membrane has been established.
online pharmacy ref source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=10714945&dopt=Abstract
Life Sci. 2001 Jul 20;69(9):1085-92.
A possible indirect sympathomimetic action of metformin in the arterial vessel wall of spontanously hypertensive rats.
Lee JM, Peuler JD.
Department of Pharmacology, Midwestern University, Downers Grove, IL 60515, USA.
The antidiabetic drug metformin (MF) typically achieves only micromolar levels in plasma with normal therapeutic use. However, it is also known to accumulate in various tissues up to several times higher after standard oral dosing and we now have evidence from both in vivo and in vitro experiments with spontaneously hypertensive rats (SHR) that millimolar levels stimulate release of norepinephrine (NE) from vascular sympathetic nerve endings (SNEs). As shown in the present work with SHR tail arterial tissue (rich in SNEs), the known vasodilator effect of millimolar levels of MF on the smooth muscle (even if contracted with a nonadrenergic agonist), is attenuated by the presence of the SNEs unless phentolamine (an alpha receptor blocker) is present. We reasoned that the mechanism for this apparent NE-releasing action of MF is not exocytotic release as that would require depolarization of the neuronal cell membranes in SNEs, and MF at millimolar levels is known to repolarize (not depolarize) membranes of other cells. Thus, we tested the possibility that MF releases NE by an indirect sympathomimetic-like action. Such an action should be amplified by monoamine oxidase inhibitors (e.g. iproniazid) and blocked by NE-carrier inhibitors (e.g. desipramine). Accordingly, we found that the abovementioned attenuating effect of intact SNEs on MF's relaxation of SHR tail arterial tissue (compared to tissues in which SNEs were experimentally removed with 6-hydroxydopamine) was amplified nearly 3-fold by iproniazid (p<0.05) and blocked by desipramine (p<0.05). These results support an indirect sympathomimetic action of MF and raise the question whether commonly used antidepressants with properties similar to iproniazid and desipramine might alter MF's beneficial vasodilatory (and thus antihypertensive) effectiveness in diabetic patients with hypertension.
online pharmacy ref source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11508651&dopt=Abstract
Res Commun Chem Pathol Pharmacol. 1992 Oct;78(1):113-6.
In vivo glycogen and lipid synthesis by various tissues from normal and metformin-treated KK mice.
Jyothirmayi GN, Jayasundaramma B, Reddi AS.
Department of Medicine, UMDNJ-New Jersey Medical School, Neward 07103.
The incorporation of [14C] U-glucose into glycogen by liver, kidney and skeletal muscle and that into total lipid by adipose tissue was studied in noninsulin-dependent genetically diabetic KK mice treated either with metformin (50 mg/kg) or water for 10 weeks. Results show that glycogen synthesis was increased in the skeletal muscle from metformin-treated mice. Liver and kidney glycogen synthesis was not affected by metformin. Glucose incorporation was significantly increased into lipid in metformin-treated mice. Insulin administration stimulated lipid synthesis in adipose tissue, but had no effect on muscle glycogen synthesis in metformin-treated mice. These data suggest that chronic metformin treatment potentiates the endogenous insulin action on glucose in skeletal muscle and adipose tissue, and thus confirm our previous results of increased glycogen synthesis by skeletal muscle in metformin-treated KK mice.
online pharmacy ref source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=1462045&dopt=Abstract
online pharmacies ||
Hair Million herbal formula for hair loss and hair growth ||
Amoxicillin ||
Tramadol ||
Paxil ||
Rx Drugs USA, Prescription Drugs Online Pharmacy ||
Zithromax ||
online pharmacy ||
Antibiotics and prescription medications online literature ||
Antibiotics