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Species differences in the formation of DA‐8164 after intravenous and/or oral administration of DA‐8159, a new erectogenic, to mice, rats, rabbits, dogs and humans
Author(s) -
Shim Hyun J.,
Kim Yu C.,
Lee Joo H.,
Park Kyung J.,
Kwon Jong W.,
Kim Won B.,
Lee Myung G.
Publication year - 2005
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.444
Subject(s) - oral administration , pharmacokinetics , pharmacology , chemistry , fissipedia , route of administration , plasma concentration , area under the curve , medicine
Species differences in the formation of DA‐8164 after intravenous and/or oral administration of DA‐8159 to mice, rats, rabbits, dogs and humans were investigated. After intravenous administration of DA‐8159, the formation of DA‐8164 decreased in the order mice, rats, rabbits and dogs; the AUC DA‐8164 / AUC DA‐8159 ratios were 0.479, 0.199, 0.0452 and close to 0 (DA‐8164 was below the detection limit in dog plasma), respectively. After oral administration of DA‐8159, the formation of DA‐8164 was considerable in mice, rats and humans, but almost negligible in dogs; the AUC (or AUC 0–t ) DA‐8164 / AUC (or AUC 0–t ) DA‐8159 ratios were 2.99, 2.67, 1.39 and 0.0650, respectively. The above data suggested that the formation of DA‐8164 was almost negligible after both intravenous and oral administration in dogs. The species differences for the formation of DA‐8164 may be due to the involvement of different CYP isozymes for each species and/or a different amount or activity of CYP isozyme if the same CYP isozyme is involved for the formation of DA‐8164 for all species. The AUC (or AUC 0–t ) DA‐8164 / AUC (or AUC 0–t ) DA‐8159 ratios after oral administration were greater than those after intravenous administration in mice, rats and dogs, and this could be due to considerable first‐pass (gastric, intestinal and/or hepatic) effects in the species as proved in rats. Copyright © 2005 John Wiley & Sons, Ltd.