Zanamivir Oral Delivery: Enhanced Plasma and Lung Bioavailability in Rats

Title
Zanamivir Oral Delivery: Enhanced Plasma and Lung Bioavailability in Rats
Author(s)
김종오Srinivasan Shanmugam[Srinivasan Shanmugam]우종수[우종수]임호택[임호택]김경수[김경수]손영택[손영택]용철순최한곤[최한곤]김용일[김용일]
Keywords
INFLUENZA-A VIRUS; INTESTINAL-ABSORPTION; PERMEATION ENHANCERS; DRUG-DELIVERY; SODIUM CAPRATE; CLINICAL-APPLICATIONS; HEALTHY-VOLUNTEERS; RECTAL ABSORPTION; CACO-2 MONOLAYERS; SALMON-CALCITONIN
Issue Date
201303
Publisher
KOREAN SOC APPLIED PHARMACOLOGY
Citation
BIOMOLECULES & THERAPEUTICS, v.21, no.2, pp.161 - 169
Abstract
The objective of this study was to enhance the oral bioavailability (BA) of zanamivir (ZMR) by increasing its intestinal permeability using permeation enhancers (PE). Four different classes of PEs (Labrasol (R), sodium cholate, sodium caprate, hydroxypropyl beta-cyclodextrin) were investigated for their ability to enhance the permeation of ZMR across Caco-2 cell monolayers. The flux and P-app of ZMR in the presence of sodium caprate (SC) was significantly higher than other PEs in comparison to control, and was selected for further investigation. All concentrations of SC (10-200 mM) demonstrated enhanced flux of ZMR in comparison to control. The highest flux (13 folds higher than control) was achieved for the formulation with highest SC concentration (200 mM). The relative BA of ZMR formulation containing SC (PO-SC) in plasma at a dose of 10 mg/kg following oral administration in rats was 317.65% in comparison to control formulation (PO-C). Besides, the AUC(0-24) (h) of ZMR in the lungs following oral administration of PO-SC was 125.22 +/- 27.25 ng hr ml(-1) with a C. of 156.00 +/- 24.00 ng/ml reached at 0.50 +/- 0.00 h. But, there was no ZMR detected in the lungs following administration of control formulation (PO-C). The findings of this study indicated that the oral formulation PO-SC containing ZMR and SC was able to enhance the BA of ZMR in plasma to an appropriate amount that would make ZMR available in lungs at a concentration higher (>10 ng/ml) than the IC50 concentration of influenza virus (0.64-7.9 ng/ml) to exert its therapeutic effect.
URI
http://hdl.handle.net/YU.REPOSITORY/26277http://dx.doi.org/10.4062/biomolther.2013.010
ISSN
1976-9148
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약학대학 > 약학부 > Articles
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