title: 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.
abstract: 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.
authors.affiliation: College of Pharmacy and Research Institute of Pharmaceutical Sciences, Seoul National University, San 56-1, Shinlim-Dong, Kwanak-Gu, Seoul 151-742, Republic of Korea.
authors.forename: Hyun J
authors.initials: HJ
authors.lastname: Shim
authors.forename: Yu C
authors.initials: YC
authors.lastname: Kim
authors.forename: Joo H
authors.initials: JH
authors.lastname: Lee
authors.forename: Kyung J
authors.initials: KJ
authors.lastname: Park
authors.forename: Jong W
authors.initials: JW
authors.lastname: Kwon
authors.forename: Won B
authors.initials: WB
authors.lastname: Kim
authors.forename: Myung G
authors.initials: MG
authors.lastname: Lee
mesh_terms: D000284:Administration, Oral; D000818:Animals; D019540:Area Under Curve; D001682:Biological Availability; D002851:Chromatography, High Pressure Liquid; D004285:Dogs; D006801:Humans; D007262:Infusions, Intravenous; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D010410:Penile Erection / Q000187:drug effects*; D011743:Pyrimidines / Q000008:administration & dosage / Q000097:blood / Q000378:metabolism* / Q000493:pharmacokinetics*; D011817:Rabbits; D051381:Rats; D017207:Rats, Sprague-Dawley; D013045:Species Specificity; D013449:Sulfonamides; D000096926:Benzenesulfonamides
chemical_list: D011743:Pyrimidines; D013449:Sulfonamides; C502127:DA-8164; C419664:udenafil; D000096926:Benzenesulfonamides