Biomol Ther.  2013 Mar;21(2):161-169.

Zanamivir Oral Delivery: Enhanced Plasma and Lung Bioavailability in Rats

• Shanmugam
• Im HT
• Sohn YT
• Kim KS
• Kim YI
• Yong CS
• Kim JO
• Choi HG
• Woo JS

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 Papp 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 AUC0-24 h of ZMR in the lungs following oral administration of PO-SC was 125.22 +/- 27.25 ng hr ml(-1) with a Cmax 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.

Keyword

Zanamivir oral delivery; Permeation enhancer; Bioavailability enhancement; Sodium caprate; Influenza

MeSH Terms

Administration, Oral
Animals
Biological Availability*
Caco-2 Cells
Humans
Influenza, Human
Inhibitory Concentration 50
Lung*
Orthomyxoviridae
Permeability
Plasma*
Rats*
Sodium
Sodium Cholate
Zanamivir*
Sodium
Sodium Cholate
Zanamivir