title: Pharmacokinetics of intravenous and oral DA-8159, a new erectogenic, in rats with protein-calorie malnutrition.
abstract: Influence of dietary protein deficiency on the pharmacokinetics of DA-8159 and one of its metabolites, DA-8164, was investigated after intravenous and oral administration of DA-8159 at a dose of 30 mg kg(-1) to male Sprague-Dawley rats allowed free access to a 23% (control) or 5% (protein-calorie malnutrition, PCM) casein diet for 4 weeks. The total area under the plasma concentration-time curve from time zero to time infinity (AUC) values of DA-8164 were significantly smaller after both intravenous (87.0 vs 162 microg min mL(-1)) and oral (144 vs 319 microg min mL(-1)) administration of DA-8159 to PCM rats. This could be due to the decrease in CYP3A1/2 (50-60%) in the rats because DA-8164 was mainly formed via CYP3A1/2 in rats. This could be supported by significantly slower in-vitro CL(int) (2.04+/-0.646 vs 3.15+/-0.693 microL min(-1) (mg protein)(-1)) for the formation of DA-8164 in hepatic microsomal fraction of PCM rats. After intravenous administration of DA-8159, the AUC values of DA-8159 were not significantly different between the two groups of rats although the AUC of DA-8164 was significantly smaller in PCM rats, and this may be due to the minor metabolic pathway of DA-8164 in rats. However, after oral administration of DA-8159, the AUC of DA-8159 was significantly greater in PCM rats (194 vs 122 microg min mL(-1)). This was not due to enhanced absorption of DA-8159 from the gastrointestinal tract in the rats but may be due to a decreased intestinal first-pass effect of DA-8159 in the rats.
authors.affiliation: Research Laboratory, Dong-A Pharmaceutical Company, 47, Sangal-Ri, Kiheung-Up, Yongin, Kyungki-Do 449-900, 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: Byung O
authors.initials: BO
authors.lastname: Ahn
authors.forename: Jong W
authors.initials: JW
authors.lastname: Kwon
authors.forename: Won B
authors.initials: WB
authors.lastname: Kim
authors.forename: Inchul
authors.initials: I
authors.lastname: Lee
authors.forename: Myung G
authors.initials: MG
authors.lastname: Lee
mesh_terms: D000284:Administration, Oral; D000818:Animals; D007172:Erectile Dysfunction / Q000097:blood / Q000188:drug therapy*; D007262:Infusions, Intravenous; D008297:Male; D011502:Protein-Energy Malnutrition / Q000097:blood / Q000188:drug therapy*; D011743:Pyrimidines / Q000008:administration & dosage* / Q000097:blood / Q000493:pharmacokinetics*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013449:Sulfonamides; D000096926:Benzenesulfonamides
chemical_list: D011743:Pyrimidines; D013449:Sulfonamides; C419664:udenafil; D000096926:Benzenesulfonamides