Disposition of the hypolipidaemic agent, 2,3-dihydrophthalazine-1,4-dione, in Sprague Dawley rats.
The disposition of [14C]2,3-dihydrophthalazine-1,4-dione, a potent hypolipidaemic agent, has been determined after both intravenous and oral administration. Both the routes of administration afforded multi-exponential disposition with an estimated t1/2 of approximately 75 h. After oral administration, the drug was observed to be absorbed rapidly from the intestine and distributed quickly to all tissues of the body. A large quantity of the 14C-radioactivity was found in the skin and carcass. Approximately 35% of the administered radioactivity was excreted in urine after oral administration and 11% in the faeces. Approximately 66% of the radioactivity excreted in urine was the parent drug. There was evidence of an additional metabolite which accounted for 28% of the urinary radioactive excretion. The parent drug has little serum protein binding, is highly water soluble, and is probably taken up by cells by passive diffusion.
Hall
I H
IH
Division of Medicinal Chemistry and Natural Products, School of Pharmacy, University of North Carolina, Chapel Hill 27599.
Oswald
C B
CB
Wyrick
S D
SD
Maguire
J H
JH
Shrewsbury
R P
RP
D000284:Administration, Oral; D000818:Animals; D001711:Biotransformation; D002245:Carbon Dioxide / Q000378:metabolism; D055598:Chemical Phenomena; D002627:Chemistry, Physical; D005347:Fibroblasts / Q000378:metabolism; D000960:Hypolipidemic Agents / Q000378:metabolism / Q000493:pharmacokinetics* / Q000652:urine; D007275:Injections, Intravenous; D007408:Intestinal Absorption; D008165:Luminol / Q000031:analogs & derivatives / Q000378:metabolism / Q000493:pharmacokinetics* / Q000652:urine; D008297:Male; D011485:Protein Binding; D011724:Pyridazines / Q000493:pharmacokinetics*; D051381:Rats; D011919:Rats, Inbred Strains; D012995:Solubility; D013056:Spectrophotometry, Ultraviolet; D014018:Tissue Distribution
D000960:Hypolipidemic Agents; D011724:Pyridazines; D002245:Carbon Dioxide; C058828:2,3-dihydro-1,4-phthalazinedione; D008165:Luminol