Subject disposition for CELADEN study [17].

<p>Subject disposition for CELADEN study [<a href="http://www.plosntds.org/article/info:doi/10.1371/journal.pntd.0004851#pntd.0004851.ref017" target="_blank">17</a>].</p

Evolutionary relationship of the whole genome of dengue samples isolated from celgosivir treatment and placebo in relation to representative samples collected from Asia.

<p>Maximum likelihood trees were generated using the nucleotide alignment from start to stop codon of the coding region. Tip labels are coloured based on sample type, and genotypes are labelled adjacent to tip labels for DENV 2, and along branches for DENV 1 and 3. Scale bar represents nucleotide substitutions per site.</p

Predicted exposure for different dosing regimens.

<p>The Box-25th to 75^th percentile, whiskers-minimum and maximum values for the various dosing regimens is shown. (A) C_min range for the various dosing regimens shows that 150 mg every 6 hr is predicted to yield a 4.5-fold increase in median Cmin used in CELADEN trial (B) C_max, range do not vary significantly for the various dosing regimens and (C) AUC only shows a modest 1.33-fold increase over the dosing regimen used in the CELADEN trial.</p

Dependence of pharmacokinetic parameters on covariates.

<p>Body Weight (A and B); Age (C and D); Creatinine Clearance (E); and Sex (F). Clearance or volume of distribution were not significantly affected by patients’ body weight, age or sex. Drug clearance was significantly correlated with creatinine clearance, indicating a significant role of the kidneys for elimination of celgosvir. Solid line-linear regression, dashed line- 95% CI. The slope of the linear regression line of creatinine clearance versus drug clearance was 0.86 (95% CI: 0.376, 1.351).</p

PK profile of castanospermine (semi-log plot).

<p>Solid brown line is the predicted concentration of castanospermine based on the mean PK parameters and the dosing regimen studied in the trial. Gray open circles are the observed peak and trough concentrations of castanospermine. Symbols and error bars are the mean and SEM, respectively. Black dotted line is the target trough concentration (400 ng/mL) predicted based on animal efficacy studies.</p

Correlation between viremia by qPCR and plaque assay.

<p>Red filled circles–patients who received celgosivir; blue open squares–patients who received placebo; lines–linear regression to all data. Pearson correlation coefficient for all data (A)Day 1 0.79 (95% CI: 0.64 to 0.87); (B) Day 2 0.79 (95% CI: 0.65 to 0.87); (C) Day 3 0.83 (95% CI: 0.72 to 0.90); (D) Day 4 (95% CI: 0.55 to 0.83); (E) Day 5 0.36 (95% CI: 0.08 to 0.58).</p

Patient sample information.

<p>Patient sample information.</p

Sequences of primers used to amplify the DENV1 and DENV2 genome in 6 overlapping fragments.

<p>Sequences of primers used to amplify the DENV1 and DENV2 genome in 6 overlapping fragments.</p

Viremia kinetics in primary and secondary dengue patients.

<p>Log viremia Mean (± SEM) by day and prior dengue infection status. Green solid circles connected by solid line–primary dengue; open orange squares connected by dashed line–secondary dengue. Inset: VLR 2–4 by prior dengue infection status: box 25th to 75th percentile, whiskers minimum and maximum values. Virus is cleared significantly faster in secondary dengue compared to primary dengue (p = 0.002).</p

Changes in platelets and hematocrit for celgosivir (red filled circles) or placebo (blue open squares) treated patients.

<p>Mean ± SEM changes in platelets count (A) and hematocrit (B) at different study days in all patients. (C) and (D) are Mean ± SEM changes in platelets count (C) and hematocrit (D) at different study days for secondary dengue patients only. Platelet nadir values (E) and difference between maximum and minimum hematocrit values (F) for secondary dengue patients treated with celgosivir or placebo, solid line–median, bars—interquartile range.</p