Two different approaches for pharmacokinetic modeling of exhaled drug concentrations.

Th. Volk,J. I. Baumbach,A. Hauschild,T. Fink,S. Kreuer,S. Maddula

doi:10.1038/srep05423

Th. Volk, J. I. Baumbach + Show 4 more

Open Access

https://doi.org/10.1038/srep05423

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Abstract

Online measurement of drug concentrations in patient's breath is a promising approach for individualized dosage. A direct transfer from breath- to blood-concentrations is not possible. Measured exhaled concentrations are following the blood-concentration with a delay in non-steady-state situations. Therefore, it is necessary to integrate the breath-concentration into a pharmacological model. Two different approaches for pharmacokinetic modelling are presented. Usually a 3-compartment model is used for pharmacokinetic calculations of blood concentrations. This 3-compartment model is extended with a 2-compartment model based on the first compartment of the 3-compartment model and a new lung compartment. The second approach is to calculate a time delay of changes in the concentration of the first compartment to describe the lung-concentration. Exemplarily both approaches are used for modelling of exhaled propofol. Based on time series of exhaled propofol measurements using an ion-mobility-spectrometer every minute for 346 min a correlation of calculated plasma and the breath concentration was used for modelling to deliver R2 = 0.99 interdependencies. Including the time delay modelling approach the new compartment coefficient ke0lung was calculated to ke0lung = 0.27 min−1 with R2 = 0.96. The described models are not limited to propofol. They could be used for any kind of drugs, which are measurable in patient's breath.

Highlights

Online measurement of drug concentrations in patient’s breath is a promising approach for individualized dosage
During induction of anaesthesia the exhaled propofol concentration increased with a time delay compared to the target controlled infusion (TCI) plasma concentration
Y527.7*x2 1 9.64*x 1 0, where y is the lung compartment concentration and x the propofol peak intensity. In this manuscript two different pharmacological models are presented for the description of the pharmacokinetic of exhaled drug concentrations

Summary

Introduction

Online measurement of drug concentrations in patient’s breath is a promising approach for individualized dosage. A 3-compartment model is used for pharmacokinetic calculations of blood concentrations. The second approach is to calculate a time delay of changes in the concentration of the first compartment to describe the lung-concentration Both approaches are used for modelling of exhaled propofol. Based on time series of exhaled propofol measurements using an ion-mobility-spectrometer every minute for 346 min a correlation of calculated plasma and the breath concentration was used for modelling to deliver R250.99 interdependencies. The blood concentration depends on the liberation, absorption, distribution, metabolism and the excretion of the drug These factors are influenced by normal variability of the individual, genetic influences in cytochrome P450 system and organ dysfunctions. One value each minute with 1 minute retarding will be considered as provided by an experimental breath analysis method

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