*2.5. Pharmacokinetic Analysis*

Basic PK parameters of tiropramide were obtained from non-compartmental analysis (NCA) through the Phoenix-WinNonlin (8.1 version, Pharsight, Certara Inc., Princeton, NJ, USA) program. Peak plasma concentration (Cmax) and the time to reach Cmax (Tmax) were individually determined using plasma concentration–time curve. The area under the curve (AUC0–∞) was calculated as the sum of AUC0–t and Clast/k, where Clast is the final measured concentration and k is the elimination rate constant at terminal phase. AUC0–t was calculated using a linear trapezoidal rule from 0 to t (as 24) h after administration. The half-life (t1/2) was calculated as 0.693/k, and the volume of the distribution (Vd/F) was calculated as dose/k·AUC0–∞. The clearance (CL/F) was calculated by dividing the dose of tiropramide by AUC0–∞, where F is the bioavailability of oral administration. All PK parameter values were calculated as mean ± SD, and the statistical differences in the group parameters (according to genotype) were confirmed by the analysis of variance (ANOVA) through the Statistical Package for the Social Sciences (SPSS) program (23 version, IBM). A *p*-value < 0.05 was established as being statistically significant.
