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KMID : 0941820170270040258
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Korean Journal of Clinical Pharmacy
2017 Volume.27 No. 4 p.258 ~ p.266
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Influence of Oxygen to Population Pharmacokinetics/Pharmacodynamics of Alcohol in Healthy Volunteers
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Song Byung-Jeong
Back Hyun-Moon
Hwang Si-Young
Chae Jung-Woo
Yun Hwi-Yeol
Kwon Kwang-Il
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Abstract
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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®). 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. 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 of temporary 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 that this PK/PD model was robust and has good precision.
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KEYWORD
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Alcoho, pharmacokinetics, pharmacodynamics, NONMEM
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