Zanamivir Oral Delivery: Enhanced Plasma and Lung Bioavailability in Rats

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.

A Prospective Study on the Pharmacokinetics of Monoclonal-antibody-purified Factor VIII Concentrate (GreenMono (R)) in Previously Treated Subjects with Hemophilia A / 대한혈액학회지

BACKGROUND: GreenMono (R) is a plasma-derived factor VIII concentrate produced by Greencross PD based on a license of Baxters monoclonal antibody technology. The purpose of this prospective study was to document the pharmacokinetics and the acute safety of the drug. METHODS: Pharmacokinetic analysis was performed in 13 previously treated patients with hemophilia A after administration of GreenMono (R) with dose of 50units/kg. The adverse effects were observed, and changes of laboratory tests, including complete blood counts, liver and kidney function tests, urinalysis, were assessed 48 hours after the drug administration. Bethesda assay for inhibitors to factor VIII were performed on 3-7 days. RESULTS: The recovery rate of GreenMono (R) was 99+-22% (range, 71~136%), and plasma beta half life analysed by 2-compartment model was 15.7+-6.6 hours (range, 9.7~35.9 hours). No clinically significant immediate adverse effects were observed after administration of GreenMono (R). No significant change in laboratory tests were observed after administration of GreenMono (R). Inhibitors to factor VIII were maintained below 0.6 BU. CONCLUSION: GreenMono (R) is effective in pharmacokinetic analysis, and is safe without any immediate adverse effect.