Papaverine topical gel for treatment of erectile dysfunction

Intracavernous injection of vasoactive substances has been shown to be an effective means of treatment of organic erectile dysfunction. However, up to 50% of men eventually discontinue treatment often because of lack of spontaneity and needle phobia. This study was done as a phase I, placebo controlled, nonblinded investigation of the safety and efficacy of a topical papaverine gel in the treatment of erectile dysfunction. Of 20 men with organic impotence 17 completed the trial and 13 of these patients had spinal cord injuries. After application of a 15% and 20% papaverine base gel to the scrotum, perineum and penis, cavernous artery diameter was significantly increased (36%, p < 0.001) as assessed by color flow Doppler ultrasound. Peak systolic flow velocity increased 26%. Only 3 of 14 patients achieved an increase in cavernous artery diameter of 75% or more and 2 of 14 had a peak systolic flow velocity of 25 cm. per second or more after application of a topical base gel. Similar findings were present when only the patients with spinal cord injury were analyzed. The effect of a papaverine base in producing flow alterations to the penis is dose-dependent. A diminution in blood pressure was present at 15 and 30 minutes after application to the forearm, and the heart rate diminished from 68 to 62 beats per minute after application to the genitalia. No patient was symptomatic. Serum papaverine levels were not elevated over pre-application values. No hepatotoxic effects were demonstrated. Full clinical erections (mean duration 38.7 minutes) were present in 3 patients but were also present with the placebo preparation (mean duration 8.0 minutes). In conclusion, topical papaverine gel appears to be safe and well tolerated after application to the genitalia, and increases blood flow to the penis with a 15% and 20% base preparation. Minimal systemic absorption occurs and, thus, effects are probably from local absorption. Topical therapy appears to augment reflex erections in the spinal cord injury patient and may be especially beneficial in this population. Further investigation is warranted at higher concentrations or in combination with different skin absorption enhancers.