Two different approaches for pharmacokinetic modeling of exhaled drug concentrations
2014-06-24 | journal article; research paper
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- Authors
- Kreuer, S.; Hauschild, Anne-Christin ; Fink, T.; Baumbach, J. I.; Maddula, S.; Volk, Th.
- 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 R(2) = 0.99 interdependencies. Including the time delay modelling approach the new compartment coefficient k(e0lung) was calculated to k(e0lung) = 0.27 min(-1) with R(2) = 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.
- Issue Date
- 24-June-2014
- Journal
- Scientific Reports
- ISSN
- 2045-2322
- eISSN
- 2045-2322
- Language
- English