title: 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 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.
authors: Department of Anaesthesiology, Intensive Care and Pain Therapy, Saarland University Medical Center and Saarland University Faculty of Medicine, 66482 Homburg/Saar; Germany.
authors: S
authors: S
authors: Kreuer
authors: Max Planck Institute for Informatics, Research Group on Computational Systems Biology, Campus E2.1, R. 203, 66123 Saarbrücken; Germany.
authors: A
authors: A
authors: Hauschild
authors: Department of Anaesthesiology, Intensive Care and Pain Therapy, Saarland University Medical Center and Saarland University Faculty of Medicine, 66482 Homburg/Saar; Germany.
authors: T
authors: T
authors: Fink
authors: Reutlingen University, Faculty Applied Chemistry, Alteburgstrasse 150, 72762 Reutlingen; Germany.
authors: J I
authors: JI
authors: Baumbach
authors: B&S Analytik, BioMedicalCenter Dortmund, Otto-Hahn-Str. 15, 44227 Dortmund; Germany.
authors: S
authors: S
authors: Maddula
authors: Department of Anaesthesiology, Intensive Care and Pain Therapy, Saarland University Medical Center and Saarland University Faculty of Medicine, 66482 Homburg/Saar; Germany.
authors: Th
authors: T
authors: Volk
mesh_terms: D000465:Algorithms; D045853:Exhalation; D006801:Humans; D006993:Hypnotics and Sedatives / Q000097:blood / Q000493:pharmacokinetics; D007700:Kinetics; D008168:Lung / Q000378:metabolism*; D008954:Models, Biological; D015742:Propofol / Q000097:blood* / Q000493:pharmacokinetics*; D013997:Time Factors
chemical_list: D006993:Hypnotics and Sedatives; D015742:Propofol