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Subacute toxicities and toxicokinetics of a new erectogenic, DA‐8159, after single and 4‐week repeated oral administration in dogs
Author(s) -
Shim Hyun J.,
Lee Eun J.,
Kim Jung H.,
Kim Soon H.,
Kwon Jong W.,
Kim Won B.,
Cha ShinW.,
Lee Myung G.
Publication year - 2001
Publication title -
biopharmaceutics and drug disposition
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.419
H-Index - 58
eISSN - 1099-081X
pISSN - 0142-2782
DOI - 10.1002/bdd.263
Subject(s) - toxicokinetics , pharmacokinetics , oral administration , medicine , area under the curve , pharmacology , plasma concentration , route of administration , chemistry
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 ( T max ) and the dose‐normalized area under 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 0–24 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 C max and AUC 0–24 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.