title: Correlation of elimination fraction area under the curve with total body clearance.
abstract: This study attempted to determine the area under the curve ([Formula: see text]), which corresponds to the sum of all elimination processes correlated with the total clearance value. The study attempted to determine the [Formula: see text] based on the coordinates known from classic non-compartmental pharmacokinetics for a single administration of the drug. 318 pharmacokinetics profiles were used for the analysis, obtained from 220 healthy subjects over ten studies. Pharmacokinetic calculations were performed with the use of Phoenix™ WinNonlin(®) 6.3. The leave-one-out (LOO) method was used for model cross-validation. Squared cross-validated correlation coefficient (Q (2)) parameter and the difference between Q (2) and R (2) were calculated as a measure of the internal performance and model predictive ability. A high correlation between the clearance value and [Formula: see text] was demonstrated (R (2) > 0.65). However, only in the case of four studies was it possible to validate the linear model using the leave-one-out validation procedure (R (2) > 0.86). The present study proposed a method of graphical and mathematical determination of the area under the curve for the drug elimination process after a single dose of the drug. Furthermore, the concept of calculating the statistical moments and mean elimination time (MET) only for elimination processes based on [Formula: see text] was presented. The result of this work is also a new method of determining the half-life of elimination phase based on the MET value.
authors.affiliation: Polpharma Biologics, Trzy Lipy 3, 80-172, Gdańsk, Poland. tomasz.grabowski@polpharma.com.
authors.forename: Tomasz
authors.initials: T
authors.lastname: Grabowski
authors.affiliation: Polfa Warszawa S.A, Karolkowa 22/24, 01-207, Warszawa, Poland. A.Raczynska@polfawarszawa.pl.
authors.forename: Anna
authors.initials: A
authors.lastname: Raczyńska-Pawelec
authors.affiliation: Polfa Warszawa S.A, Karolkowa 22/24, 01-207, Warszawa, Poland. M.Starosciak@polfawarszawa.pl.
authors.forename: Marcin
authors.initials: M
authors.lastname: Starościak
authors.affiliation: Department of Pharmacology and Toxicology, Faculty of Veterinary Medicine, University of Warmia and Mazury in Olsztyn, Oczapowskiego 13, 10-718, Olsztyn, Poland. jerzyj@uwm.edu.pl.
authors.forename: Jerzy Jan
authors.initials: JJ
authors.lastname: Jaroszewski
mesh_terms: D019540:Area Under Curve; D006801:Humans; D008657:Metabolic Clearance Rate / Q000187:drug effects / Q000502:physiology*; D004364:Pharmaceutical Preparations / Q000008:administration & dosage / Q000378:metabolism*
chemical_list: D004364:Pharmaceutical Preparations
keywords: AUC; AUMC; Clearance; Elimination; MET; MRT