title: In search of physiologically based distribution volume estimates for macromolecules.
abstract: In their semimechanistic analysis of trastuzumab emtansine (T-DM1) pharmacokinetics, Chudasama et al., as reported in this issue, modeled the process of T-DM1 deconjugation with a series of transit compartments representing plasma volume and a single peripheral compartment. The implausibility of the two-compartment distribution model used in this study as well as in other recent attempts to analyze the distribution kinetics of trastuzumab and other macromolecules reflects the fact that this modeling has been guided primarily by statistical rather than physiological considerations.
authors.affiliation: Clinical Research Department, Pfizer, Inc., South San Francisco, California, USA.
authors.forename: P D
authors.initials: PD
authors.lastname: Garzone
authors.forename: A J
authors.initials: AJ
authors.lastname: Atkinson
mesh_terms: D000080044:Ado-Trastuzumab Emtansine; D000818:Animals; D061067:Antibodies, Monoclonal, Humanized / Q000493:pharmacokinetics* / Q000494:pharmacology; D006801:Humans; D008453:Maytansine / Q000031:analogs & derivatives* / Q000493:pharmacokinetics / Q000494:pharmacology; D008657:Metabolic Clearance Rate / Q000187:drug effects / Q000502:physiology; D008956:Models, Chemical; D000068878:Trastuzumab
chemical_list: D061067:Antibodies, Monoclonal, Humanized; D008453:Maytansine; D000068878:Trastuzumab; D000080044:Ado-Trastuzumab Emtansine