Effect of increasing zanamivir in the presence of 50 µL of Capmul MCM L8 on zanamivir absolute bioavailability after intraduodenal administration in rats.

<p>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.</p

Timecourse of changes in plasma zanamivir concentrations with differing intraduodenally administered formulations versus intravenous administration of zanamivir in PBS.

<p>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.</p

Absolute bioavailability of zanamivir after intraduodenal administration of 1.5 mg of zanamivir in 50 µL of the indicated test vehicle in rats.

<p>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.</p

Effect of increasing Capmul MCM L8 on the absolute bioavailability of 1.5 mg of zanamivir after intraduodenal administration in rats.

<p>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.</p

Summary of Pharmacokinetic Parameters for Zanamivir from Different Formulations after Intraduodenal Administration in Male Sprague-Dawley Rats at 1.5 mg/animal.

<p>C_max: Maximum plasma concentration; t_max: Time to maximum plasma concentration; t_1/2: half-life; AUC_last: Area Under the Curve, calculated to the last observable time point; AUC_∞: Area Under the Curve, extrapolated to infinity;</p>1<p>Dose normalized by dividing the parameter by the nominal dose of 1.5 mg/animal.</p

Permeability of zanamivir through Caco-2 cell monolayers in the absence and presence of absorption enhancers.

<p>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.</p

Biochemical parameters assayed from zooxanthellae isolated from corals exposed to the following six treatments and collected on Day 1 of the experiment: (1) dark, 25°C; (2) dark, 32°C; (3) low-light, 25°C; (4) low-light, 32°C; (5) high-light, 25°C; (6) high-light, 32°C.

<p>Entries in each graph give treatment untransformed means (±1 SE) and treatment bar means with different letters differed significantly at α = 0.025 using the Dunnett's Procedure.</p

Hydroxynonenal and ubiquitin assayed from isolated zooxanthellae from corals exposed to the following six treatments and collected on Day 1, Day 2, and Day 4 of the experiment: (1) dark, 25°C; (2) dark, 32°C; (3) low-light, 25°C; (4) low-light, 32°C; (5) high-light, 25°C; (6) high-light, 32°C.

<p>Entries in each graph give treatment untransformed means (±1 SE). Data were analyzed using two-way analysis of variance with a Dunnett's Procedure. Treatment means with different letters differed significantly as α = 0.025.</p

Algal density in coral nubbins maintained under six environmental treatments and sampled after 48(short term) and 127 hours (long term) after the initiation of the treatments.

<p>All treatments except dark treatments were maintained under natural dark/light cycles. Treatments include: (1) a reference irradiance treatment of 438 µmoles/meter²/second PAR peak natural irradiance using a neutral density filter (low light) at 25°C (reference temperature), (2) low light at 32°C, (3) high light (2007 µmoles/meter²/second PAR peak natural irradiance) at 25°C, (4) high light at 32°C, (5) dark at 25°C, and (6) dark at 32°C. Entries in the table give treatment means ± SE. Treatment values with different letters differed significantly at α = 0.05 using the Tukey's Honestly Signficant Difference test.</p

Representative chromatograms illustrating the peaks corresponding to the major pigments peaks denoted are chlorophyll <i>c</i>₂ (chl <i>c</i>₂) peridinin (per), cis-peridinin (cis-per), diadinoxanthin (Dd), diatoxanthin (Dt) and β-carotene (β-car) in dinoflagellates isolated from corals exposed to low light 25°C, low light 32C, high light 25°C, and high light, 32°C.

<p>Representative chromatograms illustrating the peaks corresponding to the major pigments peaks denoted are chlorophyll <i>c</i>₂ (chl <i>c</i>₂) peridinin (per), cis-peridinin (cis-per), diadinoxanthin (Dd), diatoxanthin (Dt) and β-carotene (β-car) in dinoflagellates isolated from corals exposed to low light 25°C, low light 32C, high light 25°C, and high light, 32°C.</p