Physiologically Based Kinetics Of Azt

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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