Subacute toxicities and toxicokinetics of a new erectogenic, DA-8159, after single and 4-week repeated oral administration in dogs

Citation
Sh. Shim et al., Subacute toxicities and toxicokinetics of a new erectogenic, DA-8159, after single and 4-week repeated oral administration in dogs, BIOPHARM DR, 22(3), 2001, pp. 109-117
Citations number
3
Language
INGLESE
art.tipo
Article
Categorie Soggetti
Pharmacology & Toxicology
Journal title
BIOPHARMACEUTICS & DRUG DISPOSITION
ISSN journal
0142-2782 → ACNP
Volume
22
Issue
3
Year of publication
2001
Pages
109 - 117
Database
ISI
SICI code
0142-2782(200104)22:3<109:STATOA>2.0.ZU;2-5
Abstract
The subacute toxicities and toxicokinetics of a new erectogenic, DA-8159, w ere evaluated after single (at the 1st day) and 4-week (at the 28th day) or al administration of the drug, in doses of 0 (to serve as a control), 12.5, 50 and 200 mg/kg/day, to male and female dogs (n=3 for male and female dog s for each dose). DA-8159 had an effect on the immune-related organs (or ti ssues), circulatory systems, liver, adrenal glands, ovaries and pancreas. T he toxic dose was 200 mg/kg and no observed adverse effect level was less t han 50 mg/kg for male and female dogs. There were no significant gender dif ferences in the pharmacokinetic parameters of DA-8159 for each dose after b oth single and 4-week oral administration. The pharmacokinetic parameters o f DA-8159 were dose-independent after single oral administration; the time to reach a peak plasma concentration (T-max) and the dose-normalized area u nder the plasma concentration-time curve from time zero to 24 h in plasma ( AUC(0-24) (h)) were not significantly different among three doses. However, accumulation of DA-8159 after 4-week oral administration was considerable at toxic dose, 200 mg/kg/day. For example, after 4-week administration, the dose-normalized AUC(0-24h) value at 200mg/kg/day (4.71 and 15.3 mug h/ml) was significantly greater than that at 12.5mg/kg/day. After 4-week oral adm inistration, the dose-normalized C-max and AUC(0-24h), at 200mg/kg/day were significantly higher and greater, respectively, than those after a single oral administration. Copyright (C) 2001 John Wiley & Sons, Ltd.