Disposition of the hypolipidaemic agent, 2,3-dihydrophthalazine-1,4-dione, in Sprague Dawley rats
Hall, I.H.; Oswald, C.B.; Wyrick, S.D.; Maguire, J.H.; Shrewsbury, R.P.
Journal of Pharmacy and Pharmacology 41(6): 394-397
1989
ISSN/ISBN: 0022-3573 PMID: 2570835 Document Number: 333232
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.