Exploration of PBPK Model-Calculation of Drug Time Course in Tissue Using IV Bolus Drug Plasma Concentration-Time Profile and the Physiological Parameters of the Organ.
An uncommon innovative consideration of the well-stirred linear physiologically based pharmacokinetic model and the drug plasma concentration-time profile, which is measured in routine intravenous bolus pharmacokinetic study, was applied for the calculation of the drug time course in human tissues. This cannot be obtained in the in vivo pharmacokinetic study. The physiological parameters of the organ such as organ tissue volume, organ blood flow rate, and its vascular volume were used in the calculation. The considered method was applied to calculate the time course of midazolam, alprazolam, quinidine, and diclofenac in human organs or tissues. The suggested method might be applied for the prediction of drug concentration-time profile in tissues and consequently the drug concentration level in the targeted tissue, as well as the possible undesirable toxic levels in other tissues.
Genentech Inc., 1 DNA Way, South San Francisco, California 94080. Electronic address: berezhkovskiy.leo@gene.com.
Leonid M
LM
Berezhkovskiy
D001783:Blood Flow Velocity / Q000502:physiology; D006801:Humans; D007275:Injections, Intravenous; D008954:Models, Biological; D009928:Organ Specificity; D004364:Pharmaceutical Preparations / Q000008:administration & dosage / Q000097:blood*; D010599:Pharmacokinetics; D013997:Time Factors; D014018:Tissue Distribution / Q000502:physiology
D004364:Pharmaceutical Preparations
distribution; linear pharmacokinetics; partition coefficient; physiological model; tissue partitioning; well-stirred model