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On the accuracy of a one-compartment approach for determination of drug terminal half-life



The drug terminal half-life (t1/2) is commonly predicted by a simplified one-compartment approach (t1/2 = ln 2Vss/CL), where Vss and CL are the steady-state volume of distribution and the total body clearance of drug, respectively. The analysis of the accuracy of this approach is provided. It turns out that most often a simplified one-compartment calculation underestimates t1/2 by no more than 25% for human, 26% for dog, 20% for monkey, 19% for rat, and 23% for mouse. Thus, the application of a one-compartment calculation of t1/2 is well justifiable, except for the rare cases of very high drug clearance (@@@@), where r is the equilibrium blood–plasma concentration ratio, and Q is the cardiac output. © 2013 Wiley Periodicals, Inc. and the American Pharmacists Association J Pharm Sci 102:2082–2084, 2013