Phoenix winnonlin 7

The data were analyzed using SPSS software (version 22.0, SPSS, Chicago, United States) and PLINK 1.07 (http://pngu.mgh.harvard.edu/purcell/plink/). The pharmacokinetic parameters were carried out by non-compartmental analyses (NCA) in Phoenix^® WinNonlin 7.0 software. The chi-square test (χ2-test) in PLINK software was applied to perform the Hardy-Weinberg equilibrium analysis. The measurement data were described using the mean ± SD, and the normality test was performed by Kolmogorov-Smirnov test in SPSS. Comparisons between two groups were performed using the independent samples t-test, and comparisons of differences between three groups were performed using analysis of variance (ANOVA). For non-normally distributed data, the Mann-Whitney U test was used for comparison between two groups, and the Kruskal-Wallis H was used for comparison between three groups. Logistic regression models in PLINK software were used to analyze the relationship between each genotype and sedation scores in the study population and the relationship between each genotype and the patient’s heart rate. Bonferroni correction was used for multiple testing. Power test calculations were carried out using G*Power (Version 3.1.9.4, Germany).

PK parameters were calculated with a non-compartmental model using Phoenix WinNonlin7.0 and other statistics were finished using SAS V9.4 [22 ]. Descriptive statistics including mean, standard deviation (SD), median, maximum, minimum, geometric mean, and coefficient of variation (CV) were used to summarize the PK data of time-matched concentrations and parameters. The graphs of individual C-T curve and mean C-T curve were plotted. C_max and T_max were obtained directly from the C-T curves of calcium dobesilate. AUC_0−t was calculated according to the linear trapezoidal rule. AUC_0−inf was calculated as AUC_0−t + C_t/λ_z, where C_t was the concentration at the last available point and λ_z was the slope of the linear regression of the log-transformed C-T curve. Calcium dobesilate plasma t_1/2 was calculated as 0.693/λ_z.
The major PK parameters used to evaluate the bioequivalence of these two preparations were C_max, AUC_0-t, and AUC_0-inf. ANOVA was performed on the natural logarithm (ln)-transformed major PK parameters. In the ANOVA model, sequence, treatment, and period are fixed effects, and subjects (sequence) are random effects. If the 90% CIs of test/reference geometric mean ratio (GMR) for major PK parameters were located within 80%-125% both under fasting and fed conditions, the two preparations would be considered bioequivalent [23 (link)].