Pre-clinical safety evaluation of pyrrolidine dithiocarbamate.
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.
Chabicovsky
Monika
M
MC Toxicology Consulting, Vienna, Austria.
Prieschl-Grassauer
Eva
E
Seipelt
Joachim
J
Muster
Thomas
T
Szolar
Oliver H J
OH
Hebar
Alexandra
A
Doblhoff-Dier
Otto
O
D000281:Administration, Intranasal; D000818:Animals; D000998:Antiviral Agents / Q000493:pharmacokinetics / Q000633:toxicity*; D004305:Dose-Response Relationship, Drug; D004353:Drug Evaluation, Preclinical; D005260:Female; D006321:Heart / Q000187:drug effects; D006801:Humans; D008297:Male; D051379:Mice; D009152:Mutagenicity Tests; D011759:Pyrrolidines / Q000493:pharmacokinetics / Q000633:toxicity*; D051381:Rats; D011916:Rats, Inbred F344; D017207:Rats, Sprague-Dawley; D013859:Thiocarbamates / Q000493:pharmacokinetics / Q000633:toxicity*
D000998:Antiviral Agents; D011759:Pyrrolidines; D013859:Thiocarbamates; C020972:pyrrolidine dithiocarbamic acid