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,