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

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.