레바미피드 100 mg 정제의 생물학적동등성

Abstract

Rebamipide, (±)-2-(4-chlorobenzoylamino)-3-[2(1H)-quinolinon-4-yl] propionic acid, is used for mucosal protection, healing of gastroduodenal ulcers, and treatment of gastritis. It works by enhancing mucosal defense, scavenging free radicals and temporarily activating genes encoding cyclooxygenase-2. The purpose of the present study was to evaluate the bioequivalence of two rebamipide tablets, Mucosta® (Korea Otsuca Pharmaceuticals Co., Ltd.) and Mustar (Korean Drug Co., Ltd.), according to the guidelines of the Korea Food and Drug Administration (KFDA). The release of rebamipide from the two rebamipide formulations in vitro was tested using KP VIII Apparatus II method with pH 6.8 dissolution medium. Twenty six healthy male subjects, 23.46 ± 2.63 years in age and 66.62 ± 8.97 kg in body weight, were divided into two groups and a randomized 2 × 2 cross-over study was employed. After a single tablet containing 100 mg as rebamipide was orally administered, blood samples were taken at predetermined time intervals and the concentrations of rebamipide in serum were determined using HPLC with fluorescence detector. The dissolution profiles of two formulations were similar in the tested dissolution medium. The pharmacokinetic parameters such as AUCt, Cmax and Tmax were calculated, and ANOVA test was utilized for the statistical analysis of the parameters using logarithmically transformed AUCt, Cmax and untransformed Tmax. The results showed that the differences between two formulations based on the reference drug, Mucosta® were -5.08, 3.52 and -9.71% for AUCt, Cmax and Tmax, respectively. There were no sequence effects between two formulations in these parameters. The 90% confidence intervals using logarithmically transformed data were within the acceptance range of log 0.8 to log 1.25 (e.g., log 0.84~log 1.07 and log 0.90~log 1.17 for AUCt and Cmax, respectively). Thus, the criteria of the KFDA bioequivalence guideline were satisfied, indicating Mustar tablet was bioequivalent to Muscota® tablet.