title: Pharmacokinetics, stability, and blood partition of DA-8159, a new phosphodiesterase V inhibitor.
abstract: The pharmacokinetics of DA-8159, a new phosphodiesterase V inhibitor, after 1 min intravenous, 30 mg/kg, and oral, 30 mg/kg, administration of the drug to rats, the stability of DA-8159 in various pH solutions ranging from 1 to 13, and human and rat plasma and urine, and the blood partition of DA-8159 between plasma and blood cells of rabbit were evaluated. After intravenous administration, DA-8159 was eliminated fast with the mean total body clearance of 126 ml/min/kg, and was almost completely metabolized in rats; 5.98% of intravenous dose of DA-8159 were excreted unchanged in 24-hr urine. The extent of absolute oral bioavailibility of DA-8159 was approximately 25%. The apparent volume of distribution at steady state was considerably large, 15048 ml/kg, suggesting that DA-8159 has a good affinity to rat tissues. DA-8159 was relatively stable in various pH solutions, and human and rat plasma and urine for up to 48 h incubation in a water-bath shaker kept at 37 degrees C and at a rate of 50 oscillations per min. DA-8159 reached equilibrium fast (within 30 sec mixing manually) between plasma and blood cells of rabbit blood and the plasma-to-blood cell concentration ratios were independent of initial blood concentrations of DA-8159, 1, 5, and 10 microg/ml, when the rabbit whole blood was incubated for up to 120 min; the ratios were in the range of 0.662-0.812. There was no in vitro 'blood storage effect' in the plasma concentration of DA-8159.
authors.affiliation: College of Pharmacy, Seoul National University, Kwanak-Gu, South Korea.
authors.forename: H J
authors.initials: HJ
authors.lastname: Shim
authors.forename: E J
authors.initials: EJ
authors.lastname: Lee
authors.forename: S H
authors.initials: SH
authors.lastname: Kim
authors.forename: S H
authors.initials: SH
authors.lastname: Kim
authors.forename: M
authors.initials: M
authors.lastname: Yoo
authors.forename: J W
authors.initials: JW
authors.lastname: Kwon
authors.forename: W B
authors.initials: WB
authors.lastname: Kim
authors.forename: H S
authors.initials: HS
authors.lastname: Lee
authors.forename: M G
authors.initials: MG
authors.lastname: Lee
mesh_terms: D015106:3',5'-Cyclic-GMP Phosphodiesterases; D000284:Administration, Oral; D000818:Animals; D001682:Biological Availability; D054706:Cyclic Nucleotide Phosphodiesterases, Type 5; D004355:Drug Stability; D006801:Humans; D006863:Hydrogen-Ion Concentration; D066298:In Vitro Techniques; D007262:Infusions, Intravenous; D010726:Phosphodiesterase Inhibitors / Q000097:blood / Q000493:pharmacokinetics* / Q000494:pharmacology; D010727:Phosphoric Diester Hydrolases / Q000187:drug effects*; D011743:Pyrimidines; D011817:Rabbits; D051381:Rats; D017207:Rats, Sprague-Dawley; D013449:Sulfonamides; D000096926:Benzenesulfonamides
chemical_list: D015106:3',5'-Cyclic-GMP Phosphodiesterases; D054706:Cyclic Nucleotide Phosphodiesterases, Type 5; D010726:Phosphodiesterase Inhibitors; D010727:Phosphoric Diester Hydrolases; D011743:Pyrimidines; D013449:Sulfonamides; C517381:PDE5A protein, human; C517384:Pde5a protein, rat; C419664:udenafil; D000096926:Benzenesulfonamides