A valid equation for the well-stirred perfusion limited physiologically based pharmacokinetic model that consistently accounts for the blood-tissue drug distribution in the organ and the corresponding valid equation for the steady state volume of distribution.
A consistent account of the assumptions of the well-stirred perfusion limited model leads to the equation for the organ tissue that does not coincide with that often presented in books and papers. The difference in pharmacokinetic profiles calculated by the valid and the commonly used equations could be quite significant, particularly due to contribution of the organs with relatively large perfusion volume, and especially for drugs with small tissue-plasma partition coefficient and high blood-plasma concentration ratio. Application of the valid equation may result in much faster initial drop of drug plasma concentration time curve and significantly longer terminal half-life, especially for low extraction ratio drugs. An equation for the steady state volume of distribution consistent with the well-stirred model described by the valid equation is provided.
Berezhkovskiy
Leonid M
LM
Genetech Inc, 1 DNA Way, South San Francisco, California 94080, USA. berezhkovskiy.leo@gene.com
D006801:Humans; D008099:Liver / Q000378:metabolism; D008954:Models, Biological; D009928:Organ Specificity / Q000502:physiology*; D010477:Perfusion; D004364:Pharmaceutical Preparations / Q000097:blood* / Q000378:metabolism; D010599:Pharmacokinetics; D011237:Predictive Value of Tests; D014018:Tissue Distribution
D004364:Pharmaceutical Preparations