Volume of Distribution at Steady State for a Linear Pharmacokinetic System with Peripheral Elimination

作者: Leonid M. Berezhkovskiy

DOI: 10.1002/JPS.20073

关键词:

摘要: The problem of finding the steady-state volume distribution Vss for a linear pharmacokinetic system with peripheral drug elimination is considered. A commonly used equation Vss = (D/AUC)*MRT applicable only systems central (plasma) elimination. following equation, Vss = (D/AUC)*MRTint, was obtained, where AUC calculated area under time curve total concentration in plasma after intravenous (iv) administration bolus dose, D, and MRTint intrinsic mean residence time, which average spends body (system) entering systemic circulation (plasma). value cannot be found from profile an iv input if exit occurs. obtained does not contain assumption immediate equilibrium protein tissue binding organs, thus incorporates rates all possible reactions. If exits through compartment there instant between bound unbound fractions plasma, then becomes equal to MRT = AUMC/AUC, using course injection. Thus, coincides traditional one, Vss = (D/AUC)*MRT, assumptions validity this are met. Experimental methods determining MRTint, as well whether occurs, calculation tissue–plasma partition coefficient account obtained. difference traditionally true given by (D/AUC)*MRTint discussed. © 2004 Wiley-Liss, Inc. American Pharmacists Association J Pharm Sci 93:1628–1640,

参考文章(13)
David J. Cutler, Linear systems analysis in pharmacokinetics. Journal of Pharmacokinetics and Biopharmaceutics. ,vol. 6, pp. 265- 282 ,(1978) , 10.1007/BF01312266
Peter Veng Pedersen, Novel Deconvolution Method for Linear Pharmacokinetic Systems with Polyexponential Impulse Response Journal of Pharmaceutical Sciences. ,vol. 69, pp. 312- 318 ,(1980) , 10.1002/JPS.2600690316
Leslie Z. Benet, Renato L. Galeazzi, Noncompartmental Determination of the Steady‐State Volume of Distribution Journal of Pharmaceutical Sciences. ,vol. 68, pp. 1071- 1074 ,(1979) , 10.1002/JPS.2600680845
Patrick Poulin, Frank‐Peter Theil, Prediction of Pharmacokinetics Prior to In Vivo Studies. 1. Mechanism‐Based Prediction of Volume of Distribution Journal of Pharmaceutical Sciences. ,vol. 91, pp. 129- 156 ,(2002) , 10.1002/JPS.10005