RT Journal Article
SR Electronic
T1 Pharmacokinetics of o-nitroanisole in Fischer 344 rats.
JF Drug Metabolism and Disposition
JO Drug Metab Dispos
FD American Society for Pharmacology and Experimental Therapeutics
SP 527
OP 531
VO 13
IS 5
A1 M J Miller
A1 I G Sipes
A1 D F Perry
A1 D E Carter
YR 1985
UL http://dmd.aspetjournals.org/content/13/5/527.abstract
AB The pharmacokinetics and metabolism of o-nitroanisole (ONA) were studied in male Fischer 344 rats. Three dose levels of [14C]ONA (5.0, 50, or 500 mg/kg) were administered orally to rats and daily excreta were analyzed for 14C. Since the highest dose altered the urinary excretion rate of ONA, a dose of 25 mg/kg was used for subsequent pharmacokinetic studies. Following a single 25 mg/kg iv dose of [14C]ONA, blood, tissues, and excreta were collected at times ranging from 15 min to 7 days. Urinary excretion accounted for 82% of the dose by 24 hr and 86% by 7 days. Fecal excretion was 7.5% in 24 hr and 9.0% by 7 days. Fifteen min after ONA administration, most of the 14C content was found in muscle (20%), skin (10%), adipose tissue (6.8%), and blood (6.5%). All other tissues contained less than 5% of the dose. Within 8 hr, less than 1% of the dose was present in any tissue. The initial elimination t1/2 for 14C in all tissues was 1-2 hr and the terminal t1/2 was approximately 4 days. The elimination of parent ONA from blood followed first order biphasic elimination kinetics (initial t1/2 = 30 min; terminal t1/2 = 2.2 hr). Parent ONA was rapidly eliminated from all other tissues in a monophasic manner (t1/2 = 15 min to 2 hr). Skin and fat demonstrated an uptake phase prior to the elimination of parent. Only 0.5% of the dose was excreted as ONA in the urine. Urinary metabolites of ONA were predominantly conjugated compounds (63% as sulfates; 11% as glucuronides).