Bioequivalency and Pharmacokinetics of Two Clarithromycin Tablets

Clarithromycin 정제의 생물학적 동등성 및 약물동태

This study was carried out to compare the bioavailability of Hanmi clarithromycin (250 mg/tablet) with that of $Klaricid^{(R)}$ The bioavailability was examined on 20 volunteers who received a single dose (500 mg) of each drug in the fasting state in a randomized balanced 2-way crossover design. After dosing, blood samples were collected for a period of 12 hours. Plasma samples were analyzed for clarithromycin and roxithromycin(internal standard) by HPLC/Coulometric BCD. The pharmaco-kinetic parameters ($AUC_{0-l2hr}$, Cmax, Tmax, $AUC_{inf}$, Ka, Kel, $t_{1/2}$, Vd/F and Cl/F) were calculated from the plasma clarithromycin concentration-time data of each volunteer. The computer program 'WinNonlin' was used for compartmental analysis. One compartment model with first-order input, from order output with lag time, weighting factor $l/y^2$ was chosen as the appropriate pharmacokinetic model. The major pharmacokinetic parameters ($AUC_{0-l2hr},\;AUC_{inf}$, Cmax and Tmax) of Hanmi clarithromycin were $10.7\pm0.5\;{\mu}g{\cdot}hr{\cdot}ml^{-1},\;12.7\pm0.7\;{\mu}g{\cdot}hr{\cdot}ml^{-1},\;1.7\pm0.1\;{\mu}g/ml\;and\;2.0\pm0.2\;hr$, respectively, and those of $Klaricid^{(R)}\;were\;9.8\pm0.5\;{\mu}g{\cdot}hr{\cdot}ml^{-1},\;11.7\pm0.6\;{\mu}g{\cdot}hr{\cdot}ml^{-1},\;1.6\pm0.1\;{\mu}g/ml\;and\;2.1\pm0.1\;hr$, respectively. The differences in mean values of $AUC_{0-l2hr},\;AUC_{inf}$ and Cmax between two products were $9.88\%,\;8.94%\;and\;6.59\%$, respectively. The least significant differences at $\alpha=0.05$ for $AUC_{0-l2hr},\;AUC_{inf}$ and Cmax were $16.08\%,\;17.81\%\;and\;18.94\%$, respectively. Though the plasma clarithromycin concentrations of Hanmi clarithromycin were higher than those of $Klaricid^{(R)}$ at all observed times, the bioavailability of Hanmi clarithromycin appeared to be bioequivalent with that of $Klaricid^{(R)}$. The Ka, Kel, $t_{1/2}$, Vd/F and Cl/F of the Hanmi clarithromycin were $2.69\pm0.53\;hr^{-1},\;0.18\pm0.01 hr^{-1},\;3.9\;hr,\;248.8\pm11.4\;L\;and\;43.7\pm2.6\;L/hr$, respectively, and those of $Klaricid^{(R)} were 2.19\pm0.51\;hr^{-1},\;0.18\pm0.02\;hr^{-1},\;3.7\;hr,\;266.7\pm22.4\;L\;and\;45.3\pm2.8L/hr$, respectively. There were no statistically significant differences between two drugs in all pharmacokinetic parameters.