• Journal of Pharmaceutical Investigation
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• 제36권3호
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• pp.201-207
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• 2006

Acetaminophen (paracetamol), a para-aminophenol derivative, has analgesic and antipyretic properties and weak anti-inflammatory activity. The purpose of the present study was to evaluate the bioequivalence of two acetaminophen tablets, $Tylenol^{\circledR}$ ER (Janssen Korea Ltd.) and Tylicol ER (Hana Pharmaceutical Co., Ltd.), according to the guidelines of the Korea Food and Drug Administration (KFDA). The release of acetaminophen from the two acetaminophen formulations in vitro was tested using KP VIll Apparatus II method with pH 1.2 buffer solution. Twenty six healthy male subjects, $22.8{\pm}1.99$ years in age and $65.6{\pm}8.03$ 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 650 mg as acetaminophen was orally administered, blood samples were taken at predetermined time intervals and the concentrations of acetaminophen in serum were determined using HPLC with UV detector. The dissolution profiles of two formulations were similar in pH 1.2 buffer solution. 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, $Tylenol^{\circledR}$ ER, were 2.84, 1.89 and -1.36% 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 $0.987{\sim}log$ 1.08 and log $0.944{\sim}log$ 1.17 for $AUC_t$ and $C_{max}$, respectively). Thus, the criteria of the KFDA bioequivalence guideline were satisfied, indicating Tylicol ER tablet was bioequivalent to $Tylenol^{\circledR}$ ER tablet.

• Archives of Pharmacal Research
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• 제18권5호
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• pp.340-345
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• 1995

A nebumetone tablet in development $(Navuton^R)$ was tested for its bioequivalence to the erference tablet $(Uniton^R)$. Seventeen healthy Korean male subjects participated in this study. Each subject received a 1-g dose of nabumetone (2tables each) in an unbalanced, randomized, two-way crossover investigation. Serum concentrations of 6-methoxy-2-na-phthylacetic acid (6-MNA), a major metabolite of nebumetone, were measured over 120 hr interval by a high-performance liquid chromatography. The maximum serum concentration $(C_{max})$ and time to reach the maximum concentration$(T_{max})$ were read directly, but area under the serum concentration time curve from time 0 to 120 hr (AUC) and mean residence time serum curves showed multiple peaks of 6-MNA in most subjects, and the $C_{max}$ and $T_{max}$ were read from the highest serum peaks. calculated bioavailability parameters for test and reference tablets were 148.6 : 1377.9 $\mug \cdot hr/ml$ for AUC; 25.2:23.1 $\mu/ml$ for $C_{max}$; 11.8:16.4 hr for $T_{max}$, and 42.6 : 43.8 hr for MRT, respectively. The paired t-test revealed no significant differences in all the parameters between the two tablets. Analysis ofl variance (ANOVA) revealed no significant differences between groups and formulations in all the parameters ($C_{max}$ and $T_{max}$, AUC and MRT) indicating the crossover design of the experiment was properly performed. But significant differences (p<0.05) between subject/groups and periods were found for all the parameters indicating substantial intersubject and interperiodic variations for these parameters.