The metabolism and disposition of 14C-indolidan, a potent and orally active cardiotonic agent, in four species of laboratory animals.
1. The metabolism and disposition of 14C-indolidan, a potent, orally-active positive inotrope with vasodilator properties, has been studied after single dose oral administration to rats, mice, dogs and monkeys. 2. Excretion of 14C in all 4 species was mostly via the urine, largely as parent drug together with two other major metabolites. 3. The two metabolites have been isolated and identified, by mass spectroscopy and 1H-n.m.r., as a dehydro-compound, with a double bond in the pyridazanone ring, and a hydroxylated derivative of the parent drug. 4. Plasma t 1/2 values, based on 14C, were 14 h in dog, 5 h in mouse and 8 h in monkey. Plasma t 1/2 of parent drug, by h.p.l.c. was 10 h in dog, approx. 5 h in rodents, and 8 h in monkeys. 5. Tissue distribution in rats showed no accumulation in any tissue; 14C concn. in all tissues were indistinguishable from background 48 h after dosage. 14C peaked at 6-8 h for most tissues but in blood and plasma, 14C was maximal 1 h after dosing.
Bernstein
J R
JR
Department of Drug Disposition, Lilly Research Labs., Eli Lilly and Co., Indianapolis, IN 46285.
Franklin
R B
RB
D000284:Administration, Oral; D000818:Animals; D001711:Biotransformation; D002316:Cardiotonic Agents / Q000008:administration & dosage / Q000378:metabolism* / Q000493:pharmacokinetics; D004285:Dogs; D005260:Female; D006207:Half-Life; D007211:Indoles / Q000008:administration & dosage / Q000378:metabolism* / Q000493:pharmacokinetics; D008253:Macaca mulatta; D008297:Male; D051379:Mice; D000078183:Oxindoles; D011724:Pyridazines / Q000008:administration & dosage / Q000378:metabolism* / Q000493:pharmacokinetics; D051381:Rats; D011919:Rats, Inbred Strains; D013045:Species Specificity; D014018:Tissue Distribution
D002316:Cardiotonic Agents; D007211:Indoles; D000078183:Oxindoles; D011724:Pyridazines; C050325:indolidan