건강한 성인에서의 알코올의 집단 약물동태/약물동력에 미치는 산소의 영향 연구
Influence of Oxygen to Population Pharmacokinetics/Pharmacodynamics of Alcohol in Healthy Volunteers
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Objective: To develop a population pharmacokinetics (PK)/pharmacodynamics (PD) model for alcohol in healthy volunteers and toelucidate individual characteristics to affects alcohol’s PK or PD including dissolved oxygen. Methods: Following multiple intakes oftotal 540 mL alcohol (19.42 v/v%) to healthy volunteer, blood alcohol concentration was measured using a Breathe alcohol analyser(Lion SD-400 Alcolmeter®). A sequential population PK/PD modeling was performed using NONMEM (ver 7.3). Results: Eighteenhealthy volunteer were included in the study. PK model of alcohol was well explained by one-compartment model with first-orderabsorption and Michaelis-Menten elimination kinetics. Ka, V/F, Vmax, Km is 8.1 hr-1, 73.7 L, 9.65 g/hr, 0.041 g/L, respectively. Covariate analysis revealed that gender significantly influenced Vmax (Male vs Female, 9.65 g/hr vs 7.38 g/hr). PD model oftemporary systolic blood pressure decreasing effect of alcohol was explained by biophase model with inhibitory Emax model. Ke0,Imax, E0, IC50 were 0.23 hr-1, 44.9 mmHg, 138 mmHg, 0.693 g/L, respectively. Conclusion: Model evaluation results suggested thatthis PK/PD model was robust and has good precision.
Abstract
Objective: To develop a population pharmacokinetics (PK)/pharmacodynamics (PD) model for alcohol in healthy volunteers and toelucidate individual characteristics to affects alcohol’s PK or PD including dissolved oxygen. Methods: Following multiple intakes oftotal 540 mL alcohol (19.42 v/v%) to healthy volunteer, blood alcohol concentration was measured using a Breathe alcohol analyser(Lion SD-400 Alcolmeter®). A sequential population PK/PD modeling was performed using NONMEM (ver 7.3). Results: Eighteenhealthy volunteer were included in the study. PK model of alcohol was well explained by one-compartment model with first-orderabsorption and Michaelis-Menten elimination kinetics. Ka, V/F, Vmax, Km is 8.1 hr-1, 73.7 L, 9.65 g/hr, 0.041 g/L, respectively. Covariate analysis revealed that gender significantly influenced Vmax (Male vs Female, 9.65 g/hr vs 7.38 g/hr). PD model oftemporary systolic blood pressure decreasing effect of alcohol was explained by biophase model with inhibitory Emax model. Ke0,Imax, E0, IC50 were 0.23 hr-1, 44.9 mmHg, 138 mmHg, 0.693 g/L, respectively. Conclusion: Model evaluation results suggested thatthis PK/PD model was robust and has good precision.
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