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
Identifieur interne : 001749 ( Main/Exploration ); précédent : 001748; suivant : 001750A 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
Auteurs : Leonid M. Berezhkovskiy [États-Unis]Source :
- Journal of Pharmaceutical Sciences [ 0022-3549 ] ; 2010-01.
English descriptors
- Teeft :
- Accurate estimation, American pharmacists association, Average value, Average values, Berezhkovskiy, Blood cells, Blood concentration, Bolus administration, Clin pharmacol, Clint, Clintfu, Concentration ratio, Consistent account, Corg, Corg vorg, Distribution volume, Drug concentration, Drug distribution, Drug elimination, Drug extraction ratio, Drug plasma, Drug plasma concentration, Drug quantity, Drug transfer, Elimination organ, Elimination rate, Emergent blood, Equilibrium concentration ratio, Equilibrium partition, Experimental measurements, Extraction ratio drugs, Hepatic drug clearance, Human liver, Initial plasma concentration, Instantaneous equilibration, January, Large perfusion volume, Negligible difference, Organ, Organ clearance, Organ tissue, Organ tissues, Outgoing blood, Pbpk, Pbpk model, Perfusion, Perfusion volume, Perfusion volumes, Peripheral tissues, Pharm, Pharmaceutical, Pharmaceutical sciences, Pharmacokinet biopharm, Pharmacokinetic, Pharmacokinetic model, Pharmacokinetic modeling, Pharmacokinetics, Physiological parameters, Physiologically, Plasma, Plasma concentration, Plasma concentration ratio, Plasma concentrations, Plasma volume, Steady state, Steady state concentration, Steady state concentrations, Steady state condition, Steady state partition, Steady state volume, Systemic blood, Systemic circulation, Term veff, Tissue concentration, Tissue concentration time curves, Tissue concentrations, Tissue volume, Total drug concentration, Unbound drug fraction, Valid equation, Veff, Veff vorg, Volume term, Vorg, Whole organ, Whole organ volume, Whole organs.
Abstract
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. © 2009 Wiley‐Liss, Inc. and the American Pharmacists Association J Pharm Sci 99:475–485, 2010
Url:
DOI: 10.1002/jps.21798
Affiliations:
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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. © 2009 Wiley‐Liss, Inc. and the American Pharmacists Association J Pharm Sci 99:475–485, 2010</div></front></TEI><affiliations><list><country><li>États-Unis</li></country><region><li>Californie</li></region></list><tree><country name="États-Unis"><region name="Californie"><name sortKey="Berezhkovskiy, Leonid M" sort="Berezhkovskiy, Leonid M" uniqKey="Berezhkovskiy L" first="Leonid M." last="Berezhkovskiy">Leonid M. Berezhkovskiy</name></region><name sortKey="Berezhkovskiy, Leonid M" sort="Berezhkovskiy, Leonid M" uniqKey="Berezhkovskiy L" first="Leonid M." last="Berezhkovskiy">Leonid M. Berezhkovskiy</name></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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