Abstract
Famciclovir, 9-(4-hydroxy-3-hydroxymethylbut-1-yl) guanine, is an oral prodrug of the antiherpesvirus nucleoside analogue, penciclovir. In human, famciclovir is orally well absorbed and then undergoes extensive first pass metabolism to penciclovir and essentially no parent compound is recovered from plasma or urine. The purpose of the present study was to evaluate the bioequivalence of two famciclovir tablets, Famvir tablet 750 mg (Novartis Korea Ltd.) and Famcivir tablet 750 mg (Hanmi Pharmaceutical. Co., Ltd.), according to the guidelines of the Korea Food and Drug Administration (KFDA). The release of famciclovir from the two famciclovir formulations in vitro was tested using KP VIII Apparatus II method with water. Twenty six healthy male subjects, $23.38{\pm}1.72$ years in age and $68.59{\pm}7.84\;kg$ in body weight, were divided into two groups and a randomized $2{\times}2$ cross-over study was employed. After a single tablet containing 750 mg as famciclovir was orally administered, blood samples were taken at predetermined time intervals and the concentrations of penciclovir in serum were determined using HPLC with UV detector. The dissolution profiles of two formulations ere similar at water. 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, $Famvir^{(R)}$ tablet 750 mg, were -0.53%, 1.12% and -24.82% 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., $log\;0.9569{\sim}log\;1.0423$ and $log\;0.8763{\sim}log\;1.2136$ for $AUC_t$ and $C_{max}$, respectively). Thus, the criteria of the KFDA bioequivalence guideline were satisfied, indicating Famcivir tablet 750 mg was bioequivalent to Famvir tablet 750 mg.
