Dose-dependency and time-course of electrophysiologic short-term effects of VIAGRA: a case study.
The dose-dependency and time-course of the short-term visual effects of sildenafil citrate (VIAGRA) were tested in two subjects. Blood pressure was measured and samples of blood taken at 30 min intervals before and after drug administration. In the first experiment, prolongations of the implicit times of the scotopic maximum a-wave, cone a- and b-wave, 33 Hz flicker, ON-response a- and b-wave and 3.3 Hz a- and b-wave electroretinogram (ERG) recordings and of the oscillatory potentials OP1, OP2, and OP3 were observed for both eyes of both subjects, following 100 or 200 mg dosings. Interestingly, no prolongation was found for OP4, to which the OFF-bipolar cell pathway significantly contributes. In the second experiment, in which visual function was repeatedly assessed following a 200 mg dose, similar prolongations were found in both eyes of one subject for the implicit times of the oscillatory potential OP2, the cone b-wave response and the 3.3 Hz a-wave. Moreover, the steady-state (A0) and immediate extinction (B0) blue target thresholds of transient tritanopia were raised relative to the pre-drug administration baseline effects. While the maximum lowering of both systolic and diastolic blood pressure approximately correlated with the peak plasma concentration of sildenafil (c. 30-60 min after administration), the peak magnitudes of most visual effects were found at c. 110 min, consistent with a second compartment kinetic.
Jägle
Herbert
H
Department of Pathophysiology of Vision & Neuro-Ophthalmology, University Eye Hospital, Tübingen, Germany. herbert.jaegle@uni-tuebingen.de
Jägle
Christine
C
Sèrey
Ludwig
L
Sharpe
Lindsay T
LT
D015106:3',5'-Cyclic-GMP Phosphodiesterases / Q000037:antagonists & inhibitors; D000328:Adult; D001794:Blood Pressure / Q000187:drug effects; D003118:Color Perception / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004596:Electroretinography / Q000187:drug effects; D005500:Follow-Up Studies; D006801:Humans; D008297:Male; D010726:Phosphodiesterase Inhibitors / Q000008:administration & dosage* / Q000493:pharmacokinetics; D010879:Piperazines / Q000008:administration & dosage* / Q000493:pharmacokinetics; D011687:Purines; D012016:Reference Values; D012160:Retina / Q000187:drug effects* / Q000503:physiopathology; D000068677:Sildenafil Citrate; D013450:Sulfones; D013997:Time Factors
D010726:Phosphodiesterase Inhibitors; D010879:Piperazines; D011687:Purines; D013450:Sulfones; D000068677:Sildenafil Citrate; D015106:3',5'-Cyclic-GMP Phosphodiesterases