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Two different approaches for pharmacokinetic modeling of exhaled drug concentrations

  • 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.

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Metadaten
Author of HS ReutlingenBaumbach, Jörg Ingo
URN:urn:nbn:de:bsz:rt2-opus4-139
DOI:https://doi.org/10.1038/srep05423
eISSN:2045-2322
Erschienen in:Scientific Reports
Publisher:Nature Publishing Group
Place of publication:London
Document Type:Journal article
Language:English
Publication year:2014
Volume:4
Page Number:6
First Page:1
Last Page:6
DDC classes:610 Medizin, Gesundheit
Open access?:Ja
Licence (German):License Logo  Creative Commons - Namensnennung