Effect of DA-8159, a selective phosphodiesterase type 5 inhibitor, on electroretinogram and retinal histology in rabbits.
DA-8159, a selective inhibitor of phosphodiesterase type 5, was developed as a new drug for erectile dysfunction. The effect of DA-8159 on the electroretinogram (ERG) and the retinal histopathology were evaluated in rabbits. The ERG was performed prior to, and 1 and 5 hr after DA-8159 (5 to 30 mg/kg) administration. The plasma concentration of DA-8159 was determined at each time point, and retinal microscopic examination was also performed. There was no statistically significant ERG change at any dose or at any time. Though the 30 Hz flicker showed a prolongation of the implicit time at 5 hr after the administration of either DA-8159 15 mg or 30 mg/kg (p<0.05), but concurrent amplitude decreases were not statistically significant. At a dose of 5 mg/kg, no test drug was detected in the blood after either 1 or 5 hr. At either 15 mg/kg or 30 mg/kg, there was a dose-dependent increase in the blood concentration after 1 hr of drug administration, which decreased with time. In light and electron microscopic examinations of the retina, there was no remarkable change at any dose. These results suggest DA-8159 has a low risk potential to the retina, but further evaluation on the visual functions in human is needed.
Department of Ophthalmology, Chung-Ang University Medical School, Seoul, Korea. hkcho26@cau.ac.kr
Ho Kyun
HK
Cho
Kyung Koo
KK
Kang
Gook Jun
GJ
Ahn
Hyun Joo
HJ
Shim
Won Bae
WB
Kim
D015106:3',5'-Cyclic-GMP Phosphodiesterases / Q000037:antagonists & inhibitors*; D000818:Animals; D054706:Cyclic Nucleotide Phosphodiesterases, Type 5; D004305:Dose-Response Relationship, Drug; D004596:Electroretinography / Q000187:drug effects*; D006801:Humans; D008297:Male; D010726:Phosphodiesterase Inhibitors / Q000097:blood / Q000494:pharmacology*; D011743:Pyrimidines / Q000097:blood / Q000494:pharmacology*; D011817:Rabbits; D012160:Retina / Q000166:cytology* / Q000187:drug effects*; D013449:Sulfonamides; D000096926:Benzenesulfonamides
D015106:3',5'-Cyclic-GMP Phosphodiesterases; D054706:Cyclic Nucleotide Phosphodiesterases, Type 5; D010726:Phosphodiesterase Inhibitors; D011743:Pyrimidines; D013449:Sulfonamides; C517381:PDE5A protein, human; C419664:udenafil; D000096926:Benzenesulfonamides