A physiologically based pharmacokinetic (PBPK) model was constructed for 3'-azido-3'-deoxythymidine (AZT, Zidovudine) disposition in humans. Differential equations were written to describe absorption, distribution, metabolism and elimination occurring in organs and tissues. The physiological and biochemical parameters employed in the model were obtained from the literature. Partition coefficients from blood into tissue compartments were calculated based on the n-octanol/water partition coefficient of AZT. The model predicted drug concentrations in blood and several organs. Close agreement was obtained between experimental pharmacokinetic data and AZT concentrations predicted by the PBPK model. These results demonstrate the rationale use of PBPK modeling for the prediction of tissue and organ concentrations. The model can be used to develop individualized exposure regimens to obtain specific concentrations in specific tissues based upon measured values for the individual. This is illustrated in a hypothetical drug regimen example

Agency
National Institute of Health (NIH)
Institute
National Institute of Environmental Health Sciences (NIEHS)
Type
Intramural Research (Z01)
Project #
1Z01ES046009-02
Application #
6681942
Study Section
(NIEH)
Project Start
Project End
Budget Start
Budget End
Support Year
2
Fiscal Year
2002
Total Cost
Indirect Cost
Name
U.S. National Inst of Environ Hlth Scis
Department
Type
DUNS #
City
State
Country
United States
Zip Code