The acute toxicity of BIOLF-143 in the rat.
BIOLF-143, an experimental, purine-based acyclic nucleoside, was administered by iv or ip injection to young, adult, male and female Sprague-Dawley rats in order to determine the (1) pharmacokinetic disposition, (2) route and rate of excretion, and (3) acute toxicity. HPLC analysis of plasma, hepatic, and renal tissue levels was conducted following iv injections of 50 and 100 mg/kg and ip injections of 500 mg/kg. Metabolism/excretion studies were conducted following ip injections of BIOLF-143 (100 mg/kg). The assessment of acute toxicity was done following the ip injection of agent (250 mg/kg/hr for 8 consecutive hr). BIOLF-143 was rapidly distributed in the body, the estimated half-life in blood plasma being 18-23 min. The molecule was essentially unbound to plasma proteins (99% free) and was excreted unchanged in the urine. The recovery of the parent compound was 74.3 +/- 5.9% and 88.5 +/- 15.9% for male and female rats, respectively, with no metabolites or unidentifiable peaks being detected in HPLC chromatograms. No overt toxicity or untoward signs of latent toxicity were observed in the animals receiving doses up to 2000 mg/kg ip. No residues were detected in tissues at 24 hr post-treatment. A potential target organ in subchronic studies might be the kidney. High residue levels of BIOLF-143 were detected 1.0 hr post-treatment; however, the organ had cleared all residues by 24 hr after administration.
Ecobichon
D J
DJ
Department of Pharmacology and Therapeutics, McGill University, Montreal, Quebec, Canada.
Mekhael
K M
KM
Major
P
P
Ogilvie
K K
KK
D000212:Acyclovir / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000493:pharmacokinetics / Q000633:toxicity; D000818:Animals; D000998:Antiviral Agents / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000633:toxicity*; D002851:Chromatography, High Pressure Liquid; D004350:Drug Residues / Q000032:analysis; D005243:Feces / Q000032:analysis; D005260:Female; D007274:Injections, Intraperitoneal; D007275:Injections, Intravenous; D008297:Male; D051381:Rats; D011919:Rats, Inbred Strains; D014018:Tissue Distribution
D000998:Antiviral Agents; C055482:BIOLF 143; D000212:Acyclovir