Pharmacokinetic profile of ITF 296 in rats and dogs.
The pharmacokinetic profile of ITF 296 was studied after a single oral or i.v. dose administered to rats and dogs. ITF 296 and its first metabolite, ITF 1124, were measured in plasma and urine by a validated HPLC method with UV detection. Similar results were obtained in both animal species. After i.v. administration, the initial decline in plasma levels (distribution phase) was rapid, followed by a slower elimination phase. After oral administration, ITF 296 was rapidly and almost completely absorbed from the gastrointestinal tract, the maximal plasma levels being reached between 10 min and 1 h after administration in both species. Only traces of the parent compound were found in the urine of the two species, suggesting that ITF 296 was extensively metabolized. Preliminary data indicate that renal excretion is the major route of elimination of the biotransformed products. The denitrated metabolite was present in plasma from the earliest sampling time after either the i.v. or the oral route. After oral administration the drug was not significantly metabolized during passage through the liver, suggesting good bioavailability. The development of ITF 296 as a new orally active nitrate is supported by its pharmacokinetic profile in rats and dogs.
Monzani
M V
MV
Italfarmaco Research Center, Milan, Italy.
Coltro
G
G
Jiritano
L
L
Sala
A
A
D000284:Administration, Oral; D000818:Animals; D048588:Benzoxazines; D001682:Biological Availability; D001711:Biotransformation; D004285:Dogs; D005260:Female; D007275:Injections, Intravenous; D008297:Male; D009566:Nitrates / Q000008:administration & dosage / Q000493:pharmacokinetics*; D010078:Oxazines / Q000008:administration & dosage / Q000493:pharmacokinetics*; D051381:Rats; D017207:Rats, Sprague-Dawley; D014665:Vasodilator Agents / Q000008:administration & dosage / Q000493:pharmacokinetics*
D048588:Benzoxazines; D009566:Nitrates; D010078:Oxazines; D014665:Vasodilator Agents; C091726:sinitrodil