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

장인진(In-Jin Chang),신재국(Jae-Gook Shin),신상구(Sang-Goo Shin),박찬웅(Chan-Woong Park),임정규(Jung-Kyoo Lim) 대한약리학회 1989 대한약리학잡지 Vol.25 No.1

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 ± 0.27 L/kg of body weight and 0.36 ± 0.08 L/kg, respectively. Vss and Vc of NAPA were 1.21 ± 0.21 L/kg and 0.26 ± 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 ± 0.08 and 0.35 ± 0.08 L/kg/hr. The half-life (t_1/2β) of procainamide and NAPA were 2.85 hrs and 2.77 hrs, respectively. Metabolic clearance (Clm)of procainamide by N-acetylation was 18.24 ± 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 0.124μg/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 ± 0.27 L/kg 및 0.36 ± 0.08 L/kg 이였으며 NAPA의 Vss및 Vd는 1.21 ± 0.21 L/kg 및 0.26 ± 0.07 L/kg이었다. 3. Procainamide 및 NAPA의 청소율(Cl)은 각 0.47 ± 0.08 L/kg/hr와 0.35 ± 0.08 L/kg/hr 이었으며 혈장 반감기(t_1/2β)는 각각 2.85 및 2.77 시간이었다. 4. N-acetylation에 의한 Procainamide의 대사청소율은 18.24 ± 6.22 ml/kg/hr로 이는 전체 procainamide 청소율의 3.9%를 차지하였다.

Pharmacokinetics of Procainamide and N-acetylprocainamide

장인진,신재국,신상구,박찬웅,임정규,Chang, In-Jin,Shin, Jae-Gook,Shin, Sang-Goo,Park, Chan-Woong,Lim, Jung-Kyoo The Korean Society of Pharmacology 1989 대한약리학잡지 Vol.25 No.1

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. 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.

Development of multifocal atrial tachycardia in a patient using aminophylline -A case report-

김이경,이철승,전준공 대한마취통증의학회 2010 Korean Journal of Anesthesiology Vol.59 No.-

An 82-year-old female, with left femoral neck fracture was scheduled for left hip hemiarthroplasty, under spinal anaesthesia. She had been suffering from diabetes, hypertension, lung cancer and was previously treated with IV aminophylline for respiratory insufficiency. She was given spinal anaesthesia with 10 mg of 0.5% hyperbaric bupivacaine, and T6 sensory block level was established. After 10 minutes, her blood pressure dropped to 80/60mmHg, so intravenous ephedrine was given. At that moment, multifocal atrial tachycardia (MAT) appeared on electrocardiogram (ECG). Intravenous infusion of phenylephrine and procainamide was given and conversion of MAT to sinus rhythm was successfully achieved. We report a case of MAT after spinal anaesthesia, in a patient with respiratory insufficiency previously treated with IV aminophylline, which was successfully treated by intravenous infusion of phenylephrine and procainamide.

프로카인아미드의 HPLC 분석법 및 한국인에서의 약동학적 특징

배정우(Jung-woo Bae),김현경(Hyun-Kyung Kim),양상인(Sang-In Yang),김지홍(Ji-Hong Kim),김경혜(Kyung-Hye Kim),장춘곤(Choon-Gon Jang),박영서(Young-Seo Park),손의동(Uy-Dong Sohn),이석용(Seok-Yong Lee) 大韓藥學會 2005 약학회지 Vol.49 No.3

Procainamide is the drug of second choice (after lidocaine) in most coronary care units for the treatment of sustained ventricular arrhythmias associated with acute myocardial infarction. The purpose of this study was to develop the efficient assay method of procainamide in human plasma and to assess the pharmacokinetic profile of procainamide in healthy Korean volunteers. The pharmacokinetics of procainamide administered orally was evaluated after a dose of 250 mg. Procainamide in plasma was assayed using a specific HPLC method with UV absorbance at 275nm. AUC was 4.58±0.90 μg/ml.hr, Cmax 1.34±0.39 μg/ml, Tmax 1.06±0.34 hr and half-life 3.07±0.34 hr. Tmax was slightly shorter than that in Caucasian (1~2hr), whereas the half-life was similar to that in Caucasian (2.5~4.1 hr).

Electro-Catalytic Behavior of an Antiarrhythmic Drug, Procainamide and its Electro-Analytical Applications

Abbar, Jyothi C.,Meti, Manjunath D.,Nandibewoor, Sharanappa T. The Korean Electrochemical Society 2018 Journal of electrochemical science and technology Vol.9 No.4

The electrocatalytic oxidative behavior of an antiarrhythmic drug, procainamide hydrochloride (PAH) at the gold electrode surface has been examined using different voltammetric methods like cyclic, linear-sweep and differential pulse voltammetry. Voltammograms obtained in this study reveal that the electrode exhibit excellent electrocatalytic activity towards oxidation of the drug. The parameters that can affect the peak current at different pH, scan rate and concentration were evaluated. The number of electrons transferred was calculated. The current displayed a wide linear response ranging from 0.5 to $30.0{\mu}M$ with a limit of detection of 56.4 nM. The impact of potential interfering agents was also studied. The electrode displayed wide advantages such as simple sample preparation, appreciable repeatability, reproducibility and also high sensitivity. Furthermore, the feasibility of the proposed method was successfully demonstrated by determining PAH in the spiked human biological sample.

5-Aminosalicylic Acid Azo-Linked to Procainamide Acts as an Anticolitic Mutual Prodrug via Additive Inhibition of Nuclear Factor kappaB

Kim, Wooseong,Nam, Joon,Lee, Sunyoung,Jeong, Seongkeun,Jung, Yunjin American Chemical Society 2016 MOLECULAR PHARMACEUTICS Vol.13 No.6

<P>To improve the anticolitic efficacy of 5-aminosalicylic acid (5-ASA), a colon-specific mutual prodrug of 5-ASA was designed. 5-ASA was coupled to procainamide (PA), a local anesthetic, via an azo bond to prepare 5-(4-{[2-(diethylamino)ethyl]carbamoyl}phenylazo)salicylic acid (5-ASA-azo-PA). 5-ASA-azo-PA was cleaved to 5-ASA and PA up to about 76% at 10 h in the cecal contents while remaining stable in the small intestinal contents. Oral gavage of 5-ASA-azo-PA and sulfasalazine, a colon-specific prodrug currently used in clinic, to rats showed similar efficiency in delivery of 5-ASA to the large intestine, and PA was not detectable in the blood after 5-ASA-azo-PA administration. Oral gavage of 5-ASA-azo-PA alleviated 2,4,6-trinitrobenzenesulfonic acid-induced rat colitis. Moreover, combined intracolonic treatment with 5-ASA and PA elicited an additive ameliorative effect. Furthermore, combined treatment with 5-ASA and PA additively inhibited nuclear factor-kappaB (NF kappa B) activity in human colon carcinoma cells and inflamed colonic tissues. Finally, 5-ASA-azo-PA administered orally was able to reduce inflammatory mediators, NF kappa B target gene products, in the inflamed colon. 5-ASA-azo-PA may be a colon-specific mutual prodrug acting against colitis, and the mutual anticolitic effects occurred at least partly through the cooperative inhibition of NF kappa B activity.</P>