Korean J Clin Pharm.  2017 Dec;27(4):258-266. 10.24304/kjcp.2017.27.4.258.

Influence of Oxygen to Population Pharmacokinetics/Pharmacodynamics of Alcohol in Healthy Volunteers

• Song B
• Back HM
• Hwang SY
• Chae JW
• Yun HY
• Kwon KI

• KMID: 2403331
• DOI: http://doi.org/10.24304/kjcp.2017.27.4.258

Abstract

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. K(a), V/F, V(max), K(m) is 8.1 hr⁻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 0.23 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.

Keyword

Alcohol; pharmacokinetics; pharmacodynamics; NONMEM