**2. Methods**

### *2.1. Study Design*

Samples obtained from a bioequivalence study of tiropramide in 24 healthy Korean males were included in this analysis. The age of these subjects ranged from 19 to 29 years (mean ± standard deviation (SD), 22.96 ± 2.61 years). Their body weights ranged from 55.2 to 82.8 kg (mean ± SD, 67.60 ± 7.28 kg). Their body surface area (BSA) ranged from 1.58 to 1.97 m<sup>2</sup> (mean ± SD, 1.80 ± 0.11 m<sup>2</sup> ), and their body mass index (BMI) ranged from 17.89 to 29.06 kg/m<sup>2</sup> (mean ± SD, 22.74 ± 2.72 kg/m<sup>2</sup> ). Each subject had no hypersensitivity to any drugs or previous history of illness and was physically normal. All subjects provided informed written consent to perform bioequivalence and PK studies. All subjects underwent physical examinations, clinical screening, complete blood count, urinalysis, and analysis of blood chemistry prior to the admission of this study to evaluate their physical health status. If subjects were taking any medications, other drugs, and/or alcohol for at least 1 week prior to this study, they were excluded from this study. The Institutional Review Board of the Institute of Bioequivalence and Bridging Study, Chonnam National University, Gwangju, Republic of Korea, reviewed and approved (Bioequivalence Test no. 875; 01.16.2003) this study protocol. Clinical studies were performed in accordance with rules of good clinical practice and the revised Declaration of Helsinki for biomedical research involving human subjects. Bioequivalence studies were performed as randomized, single-dose, open-label, crossover, and two-way studies. The data from reference formulation were only used for the current analysis. The subjects were hospitalized (Chonnam National University Hospital, Gwangju, Korea) at 7:30 p.m. 1 day before the study. The subjects had a heparin-locked catheter installed in the median cubital vein. A single dose (100 mg) of tiropramide was given orally to all subjects (after an overnight fast) in each study group with 240 mL of water. Before administration (0 h) and at 0.33, 0.67, 1, 1.5, 2, 2.5, 3, 4, 6, 8, and 12 h after oral administration, blood samples (8 mL) were collected into Vacutainer tubes. At the time of blood sampling, about 2 mL of blood was drained each time to completely remove the heparinized saline solution remaining in the IV catheter, and about 8 mL of blood was collected. Following centrifugation (for 20 min, at 5000 × *g*), plasma samples were obtained and transferred to polyethylene tubes. They were then stored at −80 ◦C until analysis. Another study was repeated in the same manner to complete the crossover design after a washout period of 7 days.
