Two different approaches for pharmacokinetic modeling of exhaled drug concentrations

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.

Calibration and validation of a MCC/IMS prototype for exhaled propofol online measurement

“…It is difficult to determine if this statistical range is tolerable for clinical measurements. Although the correlation between propofol blood and breath concentration has been described by several pharmacokinetic modeling approaches in humans [17,18], further studies are needed to design models suitable for clinical practice. The impact of an 11.3% imprecision in breath on the estimation Fig.…”

Pharmacokinetic and pharmacodynamic interactions in anaesthesia. A review of current knowledge and how it can be used to optimize anaesthetic drug administration

“…Current attempts to measure individual plasma drug concentrations at the bedside of the patient are promising but still have significant limitations. [28][29][30][31][32][33][34] In order to obtain an idea of the time course of the plasma concentration, we are limited to pharmacokinetic predictions based at best on intermittent blood sample analysis or on estimations based on current knowledge of interactions. As a consequence, the effect of a drug on the plasma concentration of another drug is currently not directly known or quantifiable by the clinician.…”

Adherence of volatile propofol to various types of plastic tubing

“…Various methods such as ion-molecule reaction mass spectrometry [4], gas chromatography mass spectrometry [5], proton transfer reaction mass spectrometry [2], selected ion flow tube mass spectrometry [6], multicapillary column ion mobility spectrometry [2,6,7], and membrane inlet ion mobility spectrometry [10] have already been successfully used to quantify propofol in exhaled air. Propofol concentrations in blood plasma and breath correlate reasonably well [3,4,9], suggesting that online measurement of exhaled propofol in breath is a possible way to personalize propofol dosing [7,[9][10][11][12][13]. Liquid propofol interacts with certain plastic materials [14][15][16][17], but the extent to which volatile propofol is absorbed from various plastics remains unknown.…”