title: The connection Between Plasma Protein Binding and Acute Toxicity as Determined by the LD50 Value.
abstract: Preclinical Research A dataset of three drug classes (acids, bases, and neutrals) with LD50 values in mice was analysed to investigate a possible connection between high plasma protein binding and acute toxicity. Initially, it was found that high plasma protein binding was associated with toxicity for acids and neutrals, but after compensating for differences in lipophilicity, plasma protein binding was found not to be associated with toxicity. The therapeutic index established by the quotient between mouse LD50 and the defined daily dose was unaffected by both lipophilicity and plasma protein binding.
authors.affiliation: Department of Pharmaceutical Biosciences, Division of Pharmaceutical Bioinformatics, Uppsala University, Uppsala, Sweden.
authors.forename: Andreas
authors.initials: A
authors.lastname: Svennebring
mesh_terms: D000143:Acids / Q000378:metabolism; D000818:Animals; D001798:Blood Proteins / Q000378:metabolism*; D062313:Databases, Pharmaceutical; D006863:Hydrogen-Ion Concentration; D007928:Lethal Dose 50; D051379:Mice; D004364:Pharmaceutical Preparations / Q000737:chemistry / Q000378:metabolism*; D011485:Protein Binding; D023382:Toxicity Tests, Acute / Q000379:methods*
chemical_list: D000143:Acids; D001798:Blood Proteins; D004364:Pharmaceutical Preparations
keywords: acute toxicity; distribution; free fraction