M Nasenh the cave. Subsequently End, the right jugular vein of rats and cannulated with a polyethylene tube. 2.4.2. Drug administration and sample collections for the nasal, meloxicam has been reached in phosphate-buffered salt solutions Solution containing 3% Tween 80 to a final concentration of 3.2 mg / ml. A dose of 1 mg / kg was in the Nasenh Chairs of rats administered through a polyethylene tube. Blood samples were withdrawn from the jugular vein before and after 2, 4, 6, 10, 20, 40, 60, 90 and 120 minutes after application. For oral administration of Wirkstoffl Solution, the 10-fold with an L Solution of phosphate salt solutions Was sung, that made for nasal administration buffered, has rats at a dose of 1 mg / kg by gavage feeding. Blood samples were withdrawn from the jugular vein before and at 10, 20, 30, 45, 60, 90 and 120 minutes after application. for intravenous s administration was the Arzneimittell solution same as that for oral administration to rats produced as a bolus injection at a dose of 1 mg / kg over one of the two poly administered thylene cannula. To avoid contamination, blood samples from the other perforated tube were measured before and after 2, 4, 6, 10, 20, 40, 60, 90 and 120 minutes removed after the application. After each sampling, an equal volume of heparinized normal saline Solution was immediately injected via the jugular catheter. The blood samples were collected at 13,000 rpm for 5 minutes and centrifuged and plasma stored at 80 ° C until analysis. 2.4.3. HPLC assay in 100 l of plasma sample were added 50 l of internal standard, followed by 100 l of 10% H3PO4 to uern the sample ANZUS. The anges Uerte mixture was then extracted with 1 ml of ethyl acetate by vortexing for 2 min.
Was After centrifugation at 3000 rpm for 10, the organic Irinotecan Camptosar layer was collected and evaporated to dryness in a vacuum concentrator. The residue was mixed with 100 l of 40% acetonitrile in 20 mM NaH2PO4 buffer Reconstituted solution. An aliquot of 20 l were injected into the HPLC for analysis. For meloxicam and lornoxicam Papp values were comparable between the three different concentrations shop. H Highest passive diffusion is probably the most important transport route for meloxicam, and lornoxicam, penetrate to the Calu-3 cell line model. Compared to the other three candidates is nebivolol lipophilic with a calculated log P of 3.7, resulting in a very small L Solubility and cellular led Re recording au Erordentlich high in Calu 3 cell line model. Such high absorption cell has entered nebivolol Born a strong cellular Re toxicity t and a low Durchl Permeability for Calu 3 cell line model. In the area of non-toxic concentration, the Papp of nebivolol has not been found in both charge lower concentrations, and Papp get the h Higher concentration was very low. Given these results, no further investigation of nebivolol was performed in Calu 3 cell line model. Further in vivo studies should, drugs with a narrow L Solubility, such as nebivolol, are very high concentrations of Co L Solvents used their L Solubility, there it can be delivered in a therapeutically useful in a volume of 25,150 liters obtained ht formulation per nostril administered. However, high L tend Solubility enhancers have the high risk of irritation of the nasal mucosa. Therefore nebiv.