건강한 성인에서의 알코올의 집단 약물동태/약물동력에 미치는 산소의 영향 연구

• Published in: 한국임상약학회지 Vol. 27; no. 4; pp. 258 - 266
• Main Authors: 송병정, 백현문, 황시영, 채정우, 윤휘열, 권광일, Song, Byungjeong, Back, Hyun-moon, Hwang, Si-young, Chae, Jung-woo, Yun, Hwi-yeol, Kwon, Kwang-il
• Format: Journal Article
• Language: Korean
• Published: 한국임상약학회 31.12.2017
• Subjects: 약학; pharmacokinetics; Alcohol; pharmacodynamics; NONMEM
• ISSN: 1226-6051; 2508-786X

Objective: To develop a population pharmacokinetics (PK)/pharmacodynamics (PD) model for alcohol in healthy volunteers and to elucidate individual characteristics to affects alcohol's PK or PD including dissolved oxygen. Methods: Following multiple intakes of total 540 mL alcohol (19.42 v/v%) to healthy volunteer, blood alcohol concentration was measured using a Breathe alcohol analyser (Lion SD-400 $Alcolmeter^{(R)}$). A sequential population PK/PD modeling was performed using NONMEM (ver 7.3). Results: Eighteen healthy volunteer were included in the study. PK model of alcohol was well explained by one-compartment model with first-order absorption and Michaelis-Menten elimination kinetics. $K_a$, V/F, $V_{max}$, $K_m$ is $8.1hr^{-1}$, 73.7 L, 9.65 g/hr, 0.041 g/L, respectively. Covariate analysis revealed that gender significantly influenced $V_{max}$ (Male vs Female, 9.65 g/hr vs 7.38 g/hr). PD model of temporary systolic blood pressure decreasing effect of alcohol was explained by biophase model with inhibitory $E_{max}$ model. $K_{e0}$, $I_{max}$, $E_0$, $IC_{50}$ were $0.23hr^{-1}$, 44.9 mmHg, 138 mmHg, 0.693 g/L, respectively. Conclusion: Model evaluation results suggested that this PK/PD model was robust and has good precision.