연구배경 : 국내에서 합성된 경구용 2세대 cephalosporin계 약물인 cefaclor. 제제(유한양행 $Cefaclor^{circledR}$)의 생체 이용률과 약동학적 특성을 기준제제인 $Ceclor^{circledR}$와 비교 검토 하였다. 방법 : 14명의 건강한 남성 지원자를 대상으로 2회에 걸쳐 cefaclor 250mg을 라틴방격법으로 무작위 교차투여 하였다. Cefaclor의 혈장농도 측정을 위해 약물 투여 후 10시간까지 혈액을 채혈하였고 농도측정을 고성능 액체크로마토그래피법을 이용하였다. 혈장농도-시간의 데이터를 non-compartment 약동학 모델을 이용하여 분석하였고 약물의 흡수속도는 nonlinear mixed effect modeling을 이용하여 1-compartment first order absorption model을 이용하여 산출하였다. 결과 : 시험제제의 생체이용률의 지표 중 흡수정도를 반영하는 AUC는 기준제제의 109.1%인 $5.28{pm}1.72{mu}g/ml{cdot}hr$였으며 기준제제에 대한 비는 $96.4{sim}123.1%$(90% 신뢰구간)의 범위로 80/125 기준에 만족하였다. Cmax는 시험제제가 유의하게 크고$(117.2{sim}153.8%)$ Tmax는 짧아$(42.4{sim}104.1%)$ 흡수가 빠른 양상을 보였으며 흡수속도상수도 90% 신뢰구간 검정에서 유의하게 큰 값을 보였다. 결론 : 이상의 시험 결과로 cefaclor 시험제제는 기준제제인 $Ceclor^{circledR}$에 비해 생체이용률의 정도는 비슷하였지만 그 흡수속도가 유의하게 큰 결과를 보였으나 이 약물의 약력학적 특성을 고려할 때 그 차이는 임상적으로 유의하지 않을 것으로 사료되었다.
Background : The bioavailability and pharmacokinetic properties of generic cefaclor($Cefaclor^{circledR}$, Yuhan Corporation), a 2nd generation oral cephalosporin, was compared to those of the reference product $Ceclor^{circledR}$. Method : Two single doses of 250mg cefaclor were administered to 14 healthy male volunteers in a balanced, randomized crossover design. Blood samples were collected serially up to 10 hours after the dose. Plasma cefaclor concentration was measured by high performance liquid chromatography. Apparent concentration-time data were analyzed by non-compartmental method. The absorption rate was determined using nonlinear mixed effect model incorporating 1-compartment first order absorption kinetics. Results : The area under the concentration time curve(AUC), which reflects the extent of drug absorption to systemic circulation, was $5.28{pm}1.72{mu}g/ml{cdot}hr$ in test formulation. This AUC value was 109.1% of the AUC of reference and was in the range of 96.4-123.1% of the reference (90% confidence interval), which was acceptable to 80/125 rule. However, Cmax of the test formulation was significantly higher(117.2-153.8%) and Tmax was shorter(42.4-104.1%) than those of the reference cefalor formulation. Absorption rate constant(ka) was also greater in test formulation$(7.19;vs;4.17hr^{-1})$. Conclusion : These results suggest that test cefaclor formulation delivers comparable extent of drug to the systemic circulation but the rate of absorption was significantly faster than reference formulation. Considering the pharmacodynamic characteristics of cephalosporins, the pharmacokinetic properties of the test formulation seem to have equivalent therapeutic outcome.
