title: On the accuracy of calculation of the mean residence time of drug in the body and its volumes of distribution based on the assumption of central elimination.
abstract: 1. The steady state and terminal volumes of distribution, as well as the mean residence time of drug in the body (Vss, Vβ, and MRT) are the common pharmacokinetic parameters calculated using the drug plasma concentration-time profile (Cp(t)) following intravenous (iv bolus or constant rate infusion) drug administration. 2. These traditional calculations are valid for the linear pharmacokinetic system with central elimination (i.e. elimination rate being proportional to drug concentration in plasma). The assumption of central elimination is not valid in general, so that the accuracy of the traditional calculation of these parameters is uncertain. 3. The comparison of Vss, Vβ, and MRT calculated by the derived exact equations and by the commonly used ones was made considering a physiological model. It turned out that the difference between the exact and simplified calculations does not exceed 2%. 4. Thus the calculations of Vss, Vβ, and MRT, which are based on the assumption of central elimination, may be considered as quite accurate. Consequently it can be used as the standard for comparisons with kinetic and in silico models.
authors.affiliation: a Genetech Inc. , South San Francisco , CA , USA.
authors.forename: Leonid M
authors.initials: LM
authors.lastname: Berezhkovskiy
mesh_terms: D006801:Humans; D007700:Kinetics; D004364:Pharmaceutical Preparations / Q000097:blood / Q000378:metabolism*; D013997:Time Factors; D014018:Tissue Distribution
chemical_list: D004364:Pharmaceutical Preparations
keywords: Central elimination; mean residence time; peripheral elimination; physiologically based pharmacokinetic model; steady state volume of distribution; terminal volume of distribution