The Efficacy, Safety and Tolerability of Intracavernous Pnu-83757 for the Treatment of Erectile Dysfunction

Abstract

Despite the introduction of sildenafil citrate many men with erectile dysfunction remain dependent on intracavernous therapy. While the majority achieves satisfactory results with currently available intracavernous preparations, all preparations have undesirable side effects, including priapism, fibrosis and post-injection pain. We determined the efficacy, safety and tolerability of the erectogenic potassium channel opener PNU-83757. We selected 66 men with erectile dysfunction of vascular etiology for intracavernous injection of PNU-83757 in a single dose, single blind, placebo controlled study. Of the 6 patients allocated into each of 11 dose groups 5 received active drug and 1 received placebo. Groups received progressive doses of PNU-83757 or placebo. Holter monitoring was performed at scheduled intervals. Heart rate, and systolic, diastolic and mean blood pressure were assessed at scheduled intervals. Blood samples were obtained for pharmacokinetic study. Patients were evaluated at regular intervals for adverse events. Investigators and patients evaluated efficacy. The first complete erection was observed at 10 mcg. Of the 25 patients receiving active drug in the 60 to 140 mcg. groups only 1 had no erectile response, 15 had partial erection and 9 had complete erection. No serious adverse events or cardiovascular effects were noted. The minimum effective dose for complete erection was 10 mcg. The erectile response reached a plateau between 60 and 140 mcg., suggesting minimal improvement in efficacy at higher doses. Patient evaluation of erectile quality corresponded well with that of investigators. PNU-83757 was efficacious and extremely well tolerated, and the only adverse events were mild. No cardiovascular side effects were observed at any dose. PNU-83757 intracavernous injections caused no post-injection pain in any patient, which may make PNU-83757 superior to alprostadil in a select group. Further study is required to evaluate the efficacy of PNU-83757 combined with other drugs and with sexual stimulation.