아트로핀 및 팜 함유 다중챔버 단일주사기 및 KMARK-1: 비글개를 이용한 단회 근육투여 비교 생체이용률 연구 = A Multi-chambered Single Autoinjector and KMARK-1 Containing Atropine and 2-PAM: Comparative Bioavailability Studies Using Single Intramuscular Injection with Beagle Dogs

다국어 초록 (Multilingual Abstract)

In this study, multi-chambered single autoinjector(2in1) and KMARK-1 containing atropine and 2-PAM(pyridine-2-aldoxime methylchloride) were administered to the beagle's muscle, and blood samples were taken for a certain period of time to compare and evaluate the pharmacokinetic profiles of the two drugs. Male beagles were used and classified into two test groups(G1, G2), and crossover pharmacokinetic studies were performed in two test groups. Blood samples were collected from the jugular vein for analysis after administration. The 90 % confidence interval(CI) for log transformed data indicated that the Cmax for both atropine(log 0.9683 ~ log 1.113) and 2-PAM(log 0.9453 ~ log 1.214) was within the limits of bioequivalence criteria, but the AUC for atropine(log 1.1786 ~ log 1.3238) failed to meet this criteria. This is expected as the amount of atropine dose is 25 % higher for the test as compared to the reference formulation. In summary, in view of the ATNAA(antidote for nerve agent of US) authorization, the Cmax equivalence was more important than AUC equivalence, so in this study, we also focused on verifying the equality of Cmax between the two autoinjectors.

참고문헌 (Reference)

1 이근우, "신경작용제 해독제 의약품 품목허가 사례 연구" 한국군사과학기술학회 19 (19): 119-126, 2016

2 안서연, "다중챔버 단일주사기: 설계, 성능 평가" 한국군사과학기술학회 20 (20): 170-180, 2017

3 Shih, T. M, "Time Course Effects of Soman on Acetylcholine and Choline Levels in Six Discrete Areas of the Rat Brain" 78 : 170-175, 1982

4 "Standard on Pharmaceutical Equivalence Study"

5 Dunn, M. A, "Progress in Medical Defence Against Nerve Agents" 262 : 649-652, 1989

6 Marino MT, "Population pharmacokinetics and pharmacodynamics of pyridostigmine Bromide for Prophylaxis Against Nerve Agents in Humans" 38 : 227-235, 1998

7 Berman, H. A, "Kinetic, Equilibrium, and Spectroscopic Studies on Dealkylation("aging")of Alkyl Organophosphonyl Acetylcholinesterase" 261 : 10646-10652, 1986

8 "KMARK-1"

9 "Guideline on Bioanalytical Method Validation"

10 ATNAA, "Clinical Pharmacology and Biopharmaceutics review(s)"

11 Lim, D. K, "Changes in ACh Levels in the Rat Brain During Subacute Administration of Diisopropylfluoro -phosphate" 90 : 477-489, 1987

12 Loomis, T. A, "Antidotal Action of Pyridinium Oximes in Anticholinesterase Poisoning ;Comparative Effects of Soman, Sarin, and Neostigmine on Neuromuscular Function" 5 : 685-701, 1963

13 "ATNAA"