Feline penile erection induced by topical glans penis application of combination alprostadil and SEPA (Topiglan)

Abstract

The objective of this study was to evaluate the efficacy of topically applied prostaglandin E1 (PGE 1 ) þ 5% SEPA (soft enhancement of percutaneous absorption) on the glans penis in a feline erection model. Erectile response after glans penis administration of PGE 1 þ 5% SEPA cream (Topiglan, MacroChem Co., Lexington, MA, USA) was compared to the erectile response after intracavernosal administration of the triple-drug combination (1.65 mg papaverine, 25 lg phentolamine, and 0.5 lg PGE 1 ). The placebo cream and increasing concentrations (0.25%, 2.5 mg/ml; 0.5%, 5 mg/ml; and 1%, 10 mg/ml) of PGE 1 þ 5% SEPA were applied in a total volume of 0.1 ml via a plastic needle-less syringe. The control triple-drug combination was administrated intracavernosally via a 30-gauge needle at the completion of each experiment to serve as a control reference. With each application of placebo, PGE 1 þ SEPA, and the triple-drug combination, changes in intracavernosal pressure and systemic blood pressure were continuously monitored. Topical application of PGE 1 þ SEPA induced increases in intracavernosal pressure in a dosedependent manner, with minimal effects on systemic blood pressure. The increases obtained with 1% PGE 1 Topiglan cream were similar to the intracavernosal pressure values elicited by the standard intracavernosal triple-drug combination. These data demonstrate that topical glans penis application of PGE 1 þ SEPA can induce an erectile response in cats with minimal systemic adverse effects. Oral pharmacological agents are the first-line treatment for male ED. Studies investigating the effectiveness of noninvasive modalities such as topical therapy should continue, because these agents have the potential to avoid the systemic effects commonly seen with oral therapies. Additionally, topical therapy may also benefit patients who are unresponsive to oral agents or have explicit contraindications. Topical PGE 1 application to the glans penis may become an important treatment option in selected patients suffering from erectile dysfunction.

Advances in the treatment of erectile dysfunction: what’s new and upcoming?

“…It consists of prostaglandin E1 (alprostadil) combined with SEPA (soft enhancer of percutaneous absorption). Topical alprostadil has been studied in cats and humans and has been shown to induce erectile responses with minimal side effects 20 . The benefit of this topical therapy is maximized when used as part of a combination regimen such as those including PDE5-Is.…”

Pharmacotherapeutic management of erectile dysfunction

“…The most promising candidates for this type of administration have been prostaglandin E1 (alprostadil) combined with SEPA (soft enhancer of percutaneous absorption), referred to as Topiglan (MacroChem, Lexington, MA), and alprostadil combined with NexACT (water‐soluble permeation enhancer), referred to as Alprox‐TD (NexMed, Robbinsville, NJ). When studied in cats and humans, topical alprostadil has been shown to induce erectile responses with minimal systemic adverse side effects, to include transient penile edema, genital pain, penile burning, and erythema . The formulation does not seem to be an effective treatment option as a single agent, but rather may be of benefit when used in combination with other medications such as PDE5 inhibitors.…”

“…When studied in cats and humans, topical alprostadil has been shown to induce erectile responses with minimal systemic adverse side effects, to include transient penile edema, genital pain, penile burning, and erythema. 71,72 The formulation does not seem to be an effective treatment option as a single agent, but rather may be of benefit when used in combination with other medications such as PDE5 inhibitors. Further clinical trials are needed to determine its importance in ED treatment.…”

Retention and migration of alprostadil cream applied topically to the glans meatus for erectile dysfunction

“…Considerable effort, therefore, has gone into formulating alprostadil into a topically applied noninvasive treatment, that is, one that does not require the insertion of a suppository into the urethra or hypodermic injection into the cavernosa. Topically applied alprostadil has been shown to increase intracavernosal pressure in a dose-dependent fashion in an animal model, 15 and to increase cavernosal artery peak systolic velocity in humans. 16 Moreover, the efficacy of topically applied alprostadil in humans has been established in several clinical trials.…”