Pre-clinical safety evaluation of pyrrolidine dithiocarbamate

Basic Clin Pharmacol Toxicol. 2010 Sep;107(3):758-67. doi: 10.1111/j.1742-7843.2010.00573.x. Epub 2010 Apr 12.

Abstract

Pyrrolidine dithiocarbamate (PDTC) was examined for its potential in the intranasal treatment of human rhinovirus infections. Prior to clinical testing, a comprehensive non-clinical programme was performed to evaluate the general toxicity of PDTC. The animal experiments included investigations in rodents with study durations ranging from single dose to repeated dosing over a period of 28 days. The routes of administration were intranasal, inhalative, oral and intravenous for single-dose toxicity and pharmacokinetic studies, and intranasal for repeated dose studies. Blood and tissue samples were obtained from PDTC-treated rats to analyse pharmacokinetics and tissue distribution. Accumulation of selected metals due to PDTC treatment was examined in liver, brain, nerves and fat tissues.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Administration, Intranasal
  • Animals
  • Antiviral Agents / pharmacokinetics
  • Antiviral Agents / toxicity*
  • Dose-Response Relationship, Drug
  • Drug Evaluation, Preclinical
  • Female
  • Heart / drug effects
  • Humans
  • Male
  • Mice
  • Mutagenicity Tests
  • Pyrrolidines / pharmacokinetics
  • Pyrrolidines / toxicity*
  • Rats
  • Rats, Inbred F344
  • Rats, Sprague-Dawley
  • Thiocarbamates / pharmacokinetics
  • Thiocarbamates / toxicity*

Substances

  • Antiviral Agents
  • Pyrrolidines
  • Thiocarbamates
  • pyrrolidine dithiocarbamic acid