Pharmacokinetics of Procainamide and N-acetylprocainamide

Procainamide와 그 대사산물(N-acetylprocainamide)의 약동학적 분석에 관한 연구

To evaluate disposition characteristics of procainamide and its active metabolite, N-acetylprocainamide (NAPA), cross-over study for procainamide and NAPA was performed in 5 male adult dogs. After single administration of 10 mg/kg procainamide over 15 minutes, the range of measured plasma NAPA concentrations during experimental period were 0.03 to 0.124 ug/ml and early 'dip' phenomenon was distinct on NAPA concentration to time curve in all 5 dogs. Volume of distribution (Vss) and central compartment volume (Vc) of procainamide were $1.20{\pm}0.27\;L/kg$ of body weight and $0.36{\pm}0.08\;L/kg$, respectively. Vss and Vc of NAPA were $1.21{\pm}0.21\;L/kg$ and $0.26{\pm}0.07\;L/kg$, respectively. Intercompartmental clearance (Clint) of procainamide was 3.44 L/kg/hr and that of NAPA was 1.62 L/kg/hr. Total body clearance (Cl) of procainamide and NAPA were $0.47{\pm}0.08$ and $0.35{\pm}0.08\;L/kg/hr$. The half-life $(t_{1/2{\beta}})$ of procainamide and NAPA were 2.85 hrs and 2.77 hrs, respectively. Metabolic clearance (Clm)of procainamide by N-acetylation was $18.24{\pm}6.22\;ml/kg/hr$, which corresponded to 3.9% of total procainamide clearance.

Procainamide를 투여후 이 약물 및 활성형 대사산물인 N-acetylprocainamide (NAPA)의 약동학적 성상을 알아보기 위해 숫컷 성견 5마리에 procainamide 및 NAPA를 교차 투여하여 얻은 혈장농도 data를 2-compartmental model에 의해 약동학적 분석을 시행하여 다음과 같은 결과를 얻었다. 1. 10mg/kg의 procainamide를 1회 15분간 정주후 혈장 procainamide 농도변화는 명백한 분포기와 소실기를 보였으며 생성된 NAPA의 혈장농도는 시간경과에 따라 최고혈장농도는 $0.124{\mu}g/ml$ 이하이었으며 정주 직후 조직분포에 따른 혈장농도의 일시적으로 감소 후 증가하는 초기 dip 현상을 보였다. 2. Procainamide의 steady-state 분포용적(Vss) 및 central compartment volume (Vc)은 각각 $1.20{\pm}0.27\;L/kg$ 및 $0.36{\pm}0.08\;L/kg$ 이였으며 NAPA의 Vss및 Vd는 $1.21{\pm}0.21\;L/kg$ 및 $0.26{\pm}0.07\;L/kg$이었다. 3. Procainamide 및 NAPA의 청소율(Cl)은 각 $0.47{\pm}0.08\;L/kg/hr$와 $0.35{\pm}0.08\;L/kg/hr$ 이었으며 혈장 반감기$(t_{1/2{\beta}})$는 각각 2.85 및 2.77 시간이었다. 4. N-acetylation에 의한 Procainamide의 대사청소율은 $18.24{\pm}6.22\;ml/kg/hr$로 이는 전체 procainamide 청소율의 3.9%를 차지하였다.