• Journal of Pharmaceutical Investigation
• /
• 제31권4호
• /
• pp.281-287
• /
• 2001

Rebamipide is a novel anti-gastric ulcer agent that has been reported to increase the synthesis of mucus, to increase the mucosal concentration of prostaglandin, and to promote rapid ulcer healing. The purpose of the present study was to evaluate the bioequivalence of two rebamipide tablets, $Mucosta^{TM}$ (Otsuka Korea Pharmaceutical Co., Ltd.) and $Rebamide^{TM}$ (Kyung Dong Pharmaceutical Co., Ltd.), according to the guidelines of Korea Food and Drug Administration (KFDA). The rebamipide release from the two rebamipide tablets in vitro was tested using KP VII Apparatus II method at pH 6.8 dissolution media. Twenty normal male volunteers, $24.20{\pm}2.26$ years in age and $66.19{\pm}9.41\;kg$ in body weight, were divided into two groups and a randomized $2{\times}2$ cross-over study was employed. After one tablet containing 100 mg of rebamipide was orally administered, blood was taken at predetermined time intervals and the concentrations of rebamipide in serum were determined using HPLC method with fluorescence detector. The dissolution profiles of two rebamipide tablets were very similar at pH 6.8 dissolution media. Besides, the pharmacokinetic parameters such as $AUC_t$, $C_{max}\;and\;T_{max}$ were calculated and ANOVA test was utilized for the statistical analysis of the parameters. The results showed that the differences in $AUC_t$, $C_{max}\;and\;T_{max}$ between two tablets based on the $Mucosta^{TM}$ were -2.57%, 5.77% and -1.47%, respectively. Minimum detectable differences $({\Delta})$ at ${\alpha}=0.05$ and $1-{\beta}=0.8$ were less than 20% (e.g., 12.62% and 17.63% for $AUC_t,\;and\;C_{max}$, respectively). The powers $(1-{\beta})$ at ${\alpha}=0.05$, ${\Delta}=0.2$ for $AUC_t\;and\;C_{max}$ were above 99.00% and 88.56%, respectively. The 90% confidence intervals were within ${\pm}20%$ (e.g., $-9.96{\sim}4.82$ and $-4.54{\sim}16.09$ for $AUC_t\;and\;C_{max}$, respectively). Two parameters met the criteria of KFDA for bioequivalence, indicating that $Rebamide^{TM}$ tablet is bioequivalent to $Mucosta^{TM}$ tablet.

• 한국임상약학회지
• /
• 제18권1호
• /
• pp.38-44
• /
• 2008

Rebamipide, ($\pm$)-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, $Mucosta^{(R)}$ (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, $23.46{\pm}2.63$ years in age and $66.62{\pm}8.97\;kg$ in body weight, were divided into two groups and a randomized $2{\times}2$ 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 $AUC_t$, $C_{max}$ and $T_{max}$ were calculated, and ANOVA test was utilized for the statistical analysis of the parameters using logarithmically transformed $AUC_t$, $C_{max}$ and untransformed $T_{max}$. The results showed that the differences between two formulations based on the reference drug, $Mucosta^{(R)}$ were -5.08, 3.52 and -9.71 % for $AUC_t$, $C_{max}$ and $T_{max}$, 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$\sim$log 1.07 and log 0.90$\sim$log 1.17 for $AUC_t$ and $C_{max}$, respectively). Thus, the criteria of the KFDA bioequivalence guideline were satisfied, indicating Mustar tablet was bioequivalent to $Mucosta^{(R)}$ tablet.