Accession Number:

AD1096307

Title:

Incorporation of Operational Features of Flight into a Physiologically-Based Pharmacokinetic (PBPK) Model

Descriptive Note:

Technical Report,01 Apr 2018,31 May 2019

Corporate Author:

711 HPW/RHMO Wright-Patterson AFB United States

Report Date:

2019-09-20

Pagination or Media Count:

100.0

Abstract:

Work was previously conducted using physiologically-based pharmacokinetic PBPK modeling and Monte Carlo analyses to estimate distributions of exposures that could result in the target exhaled breath measurements from a High-Performance Aircraft Respiratory Study HPARS. These reconstructions allowed for the determination of possible exposure distributions across a range of exposure lengths and times, or scenarios, that might be experienced by pilots during flight, but did not account for differences in pharmacokinetics due to flight conditions such as altitude and G-forces. The next step, therefore, in this ongoing work was to incorporate descriptions of physiological changes occurring as a result of flight into the existing PBPK model. The work presented here utilizes an updated PBPK model with descriptions for changes in ventilation and cardiac output due to altitude and breathing air oxygen levels as well as changes in tissue blood flows due to G-forces. The resulting PBPK model was then used to reconstruct doses for isopropanol IPA, acetone, toluene and cyclohexane based on the HPARS in a manner similar to the previous work augmented by the incorporation of physiological changes due to flight. While the predicted ranges were comparable to the previously predicted exposures with respect to STELs, the predicted exposures did show some variation from the previous values, particularly during simulated maneuvers at higher simulated G forces, thus indicating the importance of accounting for the physiological changes during flight. By expanding the current PBPK model paradigm to the physiological changes of HPA flight, a capability has been developed to assess true pilot physiology in a virtual context.

Subject Categories:

  • Biochemistry
  • Toxicology
  • Statistics and Probability

Distribution Statement:

APPROVED FOR PUBLIC RELEASE