Figure 1.
Permeability of zanamivir through Caco-2 cell monolayers in the absence and presence of absorption enhancers.
The enhancers 0.25% Capmul MCM L8 and 5% glycerol resulted in 5.2- and 5.6-fold increased permeability, respectively, compared to the no-enhancer negative control. Zanamivir had significantly higher (p<0.01) permeability in the presence of the indicated enhancers compared to the PBS control. Error bars depict standard deviation.
Figure 2.
Absolute bioavailability of zanamivir after intraduodenal administration of 1.5 mg of zanamivir in 50 µL of the indicated test vehicle in rats.
As indicated, in some experiments the test vehicles glycerol and Capmul MCM L8 were administered 2 hr prior to the administration of zanamivir in PBS. Panel A, Glycerol as test vehicle; Panel B, Capmul MCM L8 as test vehicle. Zanamivir had significantly higher (p<0.01) absolute bioavailability when dosed in the Capmul MCM L8 formulation compared to all other formulations. Error bars depict standard deviation.
Figure 3.
Timecourse of changes in plasma zanamivir concentrations with differing intraduodenally administered formulations versus intravenous administration of zanamivir in PBS.
A rapid uptake from the intraduodenally administered Capmul MCM L8 formulation was observed which was rapidly cleared in a manner corresponding to the intravenous administration route. All animals were dosed with 1.5 mg of zanamivir regardless of dosing route or formulation. Error bars depict standard deviation.
Table 1.
Summary of Pharmacokinetic Parameters for Zanamivir from Different Formulations after Intraduodenal Administration in Male Sprague-Dawley Rats at 1.5 mg/animal.
Figure 4.
Effect of increasing Capmul MCM L8 on the absolute bioavailability of 1.5 mg of zanamivir after intraduodenal administration in rats.
Zanamivir had significantly higher (p<0.01) absolute bioavailability when dosed in the Capmul MCM L8 formulation compared to the control and there was a significant difference (p<0.05) in the absolute bioavailability observed between 25 µL and 75 µL Capmul MCM L8 volume dosed groups. Error bars depict standard deviation.
Figure 5.
Effect of increasing zanamivir in the presence of 50 µL of Capmul MCM L8 on zanamivir absolute bioavailability after intraduodenal administration in rats.
Zanamivir had significantly higher (p<0.01) absolute bioavailability when dosed in the Capmul MCM L8 formulation compared to the PBS control. Error bars depict standard deviation.