title: On the accuracy of a one-compartment approach for determination of drug terminal half-life.
abstract: The drug terminal half-life (t(1/2)) is commonly predicted by a simplified one-compartment approach (t(1/2) = ln 2V(ss)/CL), where V(ss) 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 t(1/2) 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 t(1/2) is well justifiable, except for the rare cases of very high drug clearance (CL/(rQ) ≳ 0.5), where r is the equilibrium blood-plasma concentration ratio, and Q is the cardiac output.
authors.affiliation: Genentech Inc., South San Francisco, California 94080, USA. berezhkovskiy.leo@gene.com
authors.forename: Leonid M
authors.initials: LM
authors.lastname: Berezhkovskiy
mesh_terms: D000465:Algorithms; D000818:Animals; D004285:Dogs; D006207:Half-Life; D000882:Haplorhini; D006801:Humans; D008099:Liver / Q000378:metabolism; D051379:Mice; D008954:Models, Biological; D004364:Pharmaceutical Preparations / Q000097:blood* / Q000378:metabolism; D010599:Pharmacokinetics; D051381:Rats; D014018:Tissue Distribution
chemical_list: D004364:Pharmaceutical Preparations