Statistical Analysis Statistical analysis was performed using SPSS software version 11.0 (SPSS, Inc., Chicago, IL, USA).

Prior to analysis, dose-dependent parameters (Cmax and AUC) were determined using natural logarithms of individual values. For the exploration of dose proportionality, the slope β and 90% confidence intervals (CIs) obtained from the power model: ln(AUC or Cmax) = α + β × ln(dose) were computed by analysis of covariance (ANCOVA). The regression coefficient was significant at level 0.1. The pre-defined criterion was set as (0.500, 2.000),[22] and the criterion interval resulted in the value of (0.500, 1.500). The differences in pharmacokinetic parameters among dose groups were compared using ANOVA except

for tmax for which the non-parametric test (NPT) was used. Statistical INCB28060 ic50 Semaxanib mw comparisons between pharmacokinetic parameters of single and multiple doses were performed by the paired t-test (PTT), and the differences of pharmacokinetic parameters between male and female subjects were compared by the independent t-test (ITT). To determine whether steady state was reached in the multiple-dose study, the differences in Cmin,ss on days 5, 6, and 7 were compared using ANOVA. Results Study Population CB-839 mouse Healthy males and females (n = 98) participated in the FIH studies. No subject dropped out of the study. Baseline demographics of the study population are presented in table I. Single-Dose Pharmacokinetic Study The mean plasma concentration-time curves are shown in figure 2, and the main pharmacokinetic parameters

of BCQB are presented HSP90 in table III. Absorption of BCQB after intranasal administration was rapid, with a median tmax of 8 minutes for 45, 90, and 180 μg doses, and the plasma concentrations of BCQB decreased in a biphasic manner, with the mean t1/2 of 8.5 hours across the doses. Fig. 2 Mean plasma (a) and log-scaled mean plasma (b) concentration-time profiles of bencycloquidium bromide following single intranasal doses in healthy Chinese subjects. The inset expands the first 3 hours of the profile. Data are presented as mean + SD (n = 10 per dose). LLOQ = lower limit of quantitation. Table III Main pharmacokinetic parameters of bencycloquidium bromide in healthy Chinese subjects after single intranasal doses 45, 90, and 180 μga The mean and SD values of Cmax, AUCt and AUC∞ versus dose relationships after single intranasal dosing of BCQB are presented in figure 3. Over the dose range studied, the mean Cmax, AUCt and AUC∞ increased linearly across the doses by linear regression analysis, with regression equations in figure 3. Dose proportionality was observed (p > 0.