title: Time Varying Apparent Volume of Distribution and Drug Half-Lives Following Intravenous Bolus Injections.
abstract: We present a model that generalizes the apparent volume of distribution and half-life as functions of time following intravenous bolus injection. This generalized model defines a time varying apparent volume of drug distribution. The half-lives of drug remaining in the body vary in time and become longer as time elapses, eventually converging to the terminal half-life. Two example fit models were substituted into the general model: biexponential models from the least relative concentration error, and gamma variate models using adaptive regularization for least relative error of clearance. Using adult population parameters from 41 studies of the renal glomerular filtration marker 169Yb-DTPA, simulations of extracellular fluid volumes of 5, 10, 15 and 20 litres and plasma clearances of 40 and 100 ml/min were obtained. Of these models, the adaptively obtained gamma variate models had longer times to 95% of terminal volume and longer half-lives.
authors.affiliation: Department of Medical Imaging, College of Medicine, University of Saskatchewan, Saskatoon, Saskatchewan, Canada.|Department of Radiology, Memorial University of Newfoundland, St. John's, Newfoundland, Canada.
authors.forename: Carl A
authors.initials: CA
authors.lastname: Wesolowski
authors.affiliation: Department of Medical Imaging, College of Medicine, University of Saskatchewan, Saskatoon, Saskatchewan, Canada.
authors.forename: Michal J
authors.initials: MJ
authors.lastname: Wesolowski
authors.affiliation: Department of Medical Imaging, College of Medicine, University of Saskatchewan, Saskatoon, Saskatchewan, Canada.
authors.forename: Paul S
authors.initials: PS
authors.lastname: Babyn
authors.affiliation: Department of Medical Imaging, College of Medicine, University of Saskatchewan, Saskatoon, Saskatchewan, Canada.
authors.forename: Surajith N
authors.identifier: http://orcid.org/0000-0003-0939-1039
authors.initials: SN
authors.lastname: Wanasundara
mesh_terms: D000328:Adult; D005919:Glomerular Filtration Rate; D006207:Half-Life; D006801:Humans; D007275:Injections, Intravenous; D008657:Metabolic Clearance Rate; D008954:Models, Biological; D016284:Technetium Tc 99m Pentetate / Q000008:administration & dosage* / Q000037:antagonists & inhibitors / Q000493:pharmacokinetics*
chemical_list: D016284:Technetium Tc 99m Pentetate