Back to Search
Start Over
Subacute toxicities and toxicokinetics of a new erectogenic, DA-8159, after single and 4-week repeated oral administration in dogs
- Source :
- Biopharmaceutics & Drug Disposition. 22:109-117
- Publication Year :
- 2001
- Publisher :
- Wiley, 2001.
-
Abstract
- The subacute toxicities and toxicokinetics of a new erectogenic, DA-8159, were evaluated after single (at the 1st day) and 4-week (at the 28th day) oral 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 dogs for each dose). DA-8159 had an effect on the immune-related organs (or tissues), circulatory systems, liver, adrenal glands, ovaries and pancreas. The toxic dose was 200 mg/kg and no observed adverse effect level was less than 50 mg/kg for male and female dogs. There were no significant gender differences in the pharmacokinetic parameters of DA-8159 for each dose after both single and 4-week oral administration. The pharmacokinetic parameters of DA-8159 were dose-independent after single oral administration; the time to reach a peak plasma concentration (Tmax) and the dose-normalized area under the plasma concentration–time curve from time zero to 24 h in plasma (AUC0–24 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 AUC0–24 h value at 200 mg/kg/day (4.71 and 15.3 μg h/ml) was significantly greater than that at 12.5 mg/kg/day. After 4-week oral administration, the dose-normalized Cmax and AUC0–24 h at 200 mg/kg/day were significantly higher and greater, respectively, than those after a single oral administration. Copyright © 2001 John Wiley & Sons, Ltd.
- Subjects :
- Male
No-observed-adverse-effect level
Phosphodiesterase Inhibitors
Cmax
Administration, Oral
Pharmaceutical Science
Motor Activity
Pharmacology
Dogs
Erectile Dysfunction
Pharmacokinetics
Oral administration
Animals
Medicine
Toxicokinetics
Pharmacology (medical)
Sulfonamides
Time zero
biology
business.industry
Body Weight
Fissipedia
General Medicine
biology.organism_classification
Kinetics
Pyrimidines
Toxicity
Female
business
Subjects
Details
- ISSN :
- 1099081X and 01422782
- Volume :
- 22
- Database :
- OpenAIRE
- Journal :
- Biopharmaceutics & Drug Disposition
- Accession number :
- edsair.doi.dedup.....dcd1a8b00c82a410d4ea31cfe1ed16b1