Initial volume of a drug before it reaches the volume of distribution: Pharmacokinetics of F(ab′) 2 antivenoms and other drugs

Abstract

Fast disappearance of F(ab′) 2 antivenoms from the plasma compartment [Sevcik et al., 2004. Modelling Tityus scorpion venom and antivenom pharmacokinetics. Evidence of active immunoglobulin G's F(ab′) 2 extrusion mechanism from blood to tissues. Toxicon 44, 731–734; Vazquez et al., 2005. Pharmacokinetics of a F(ab′) 2 scorpion antivenom in healthy human volunteers. Toxicon 46, 797–805] suggests a quick time course to reach its final distribution volume. An equation was developed to describe how the volume occupied by a drug in the body grows with time. As discussed in the paper this equation is free of some shortcomings of an equation developed for the same purpouse by Niazi [1976. Volume of distribution as a function of time. J. Pharm. Sci. 65, 452–454]. Fluorescence microscopy showed that the rapid initial decay in plasmatic F(ab′) 2 concentration may be related to uptake of F(ab′) 2 by vascular endothelium which, in combination with accumulation in the vascular wall connective tissue, may produce an intermediate plateau in F(ab′) 2 V sl ( t), which reached its final value after 10 h. The V sl ( t) equation predicts that the plasma concentration half-time of decay has little use to estimate how a drug distributes through the body to exert its action, and predicts that, in some instances, intermediate plateaus in the time course of V sl ( t) exist. Data from the literature showed that the kinetic considerations for V sl ( t) also apply to clevidipine, digoxin, digitoxin, lidocaine and thiopentone.