Elsevier

European Urology

Volume 46, Issue 3, September 2004, Pages 357-361
European Urology

Efficacy of Sildenafil Citrate at 12 Hours after Dosing: Re-exploring the Therapeutic Window

https://doi.org/10.1016/j.eururo.2004.04.025Get rights and content

Abstract

Objective: This open-label study investigated the efficacy of sildenafil citrate at 12 hours postdose among prior treatment responders.

Patients and Methods: Eight 100-mg doses of sildenafil were provided to 40 eligible patients with erectile dysfunction (ED), who were to record the results of each sexual attempt in a patient diary. Each patient was instructed to make a sexual attempt at 1 and 12 hours postdose on 4 occasions (part 1) and only at 12 hours postdose on 4 subsequent occasions (part 2).

Results: Of 40 enrolled patients, 34 (85%) completed the study. In these evaluable patients, 97% and 74% of patients achieved erections that resulted in successful intercourse at 1 hour and 12 hours postdose, respectively. There was a nonsignificant reduction in the percentage of responders at 12 hours during part 1 versus part 2 of this study (71% versus 78%).

Conclusions: This study demonstrates that, in the majority of these patients with ED, sildenafil remains clinically active 12 hours after administration. Larger studies may be necessary to confirm and clarify the therapeutic window of sildenafil.

Introduction

The development of pharmacological agents for the treatment of erectile dysfunction (ED) has introduced greater freedom in a couples’ ability to plan sexual activity. However, couples receiving any type of pharmacological treatment for ED invariably need to “schedule” sexual activity to some degree, potentially increasing sexual encounter-related anxiety [1], [2]. In this regard, patient knowledge of specific pharmacological aspects, such as onset of action from time of administration and duration of the effect, is a prerequisite for optimal use of ED-directed therapies. Ascertaining the length of the “therapeutic window” that will allow patients with ED to successfully engage in sexual intercourse will contribute to this knowledge.

To date, the most consistent data for the onset and duration of the effects of sildenafil citrate, the first oral phosphodiesterase type 5 (PDE5) inhibitor to be developed and marketed for ED [3], were obtained from two randomized clinical trials that used the RigiScan® (Dacomed Corporation, Minneapolis, MN, USA) device to monitor changes in penile rigidity during visual sexual stimulation in a controlled hospital setting [4]. In the first study, some patients reported onset of action as quickly as 12 minutes (median of 27 minutes) after receiving sildenafil 50 mg, with the majority of patients (71%) achieving erections within 30 minutes postdose. The design of the second study was intended to demonstrate the duration of action of sildenafil at 2 and 4 hours after a 100-mg dose. When visual sexual stimulation was initiated 4 hours after dosing, 86% of patients attained erections—a response rate that was significantly higher than the corresponding rate of 31% in the placebo group. Additionally, mean duration of erections at 4 hours postdose was 17.2 minutes and 3.6 minutes for responders in the sildenafil and placebo groups, respectively [4].

The therapeutic window of sildenafil could be framed at approximately 30 minutes (median onset of action) and 4 hours (plasma half-life [t1/2]) postdose [4], [5], [6]. In clinical practice, however, we have found that patients frequently report an ability to respond to sexual stimulation >12 hours after taking sildenafil; however, the effectiveness of sildenafil beyond a 4-hour period has not been prospectively studied. Although experience with sildenafil has shown that efficacy at 4 hours postdose is adequate in most instances, a wider therapeutic window may be desirable for a minority of patients.

The objective of this open-label study was to assess the clinical activity of a single 100-mg dose of sildenafil at 12 hours postdose in patients known to respond to this therapy.

Section snippets

Eligibility and treatment

This prospective observational open-label study recruited 40 patients from a single site. Eligible patients were men older than 18 years of age who had a documented clinical diagnosis of ED based on clinical history, physical exam, and laboratory findings. The diagnosis was confirmed by a score of 21 or less on the Sexual Health Inventory for Men [7]. All patients provided informed consent to participate. All patients were undergoing sildenafil therapy for at least 3 months before entering the

Results

The 40-patient target accrual was reached. The mean ± standard deviation (S.D.) age was 54 ± 6 years, with ages ranging from 30 to 62 years. The mean ± S.D. time in treatment before entering the study was 17 ± 9 months (range 6–48 months). Most patients had mild to moderate ED (81%), and the remaining patients had severe ED (19%). In 89% of the cases, the ED etiology was considered to be organic or mixed, and 84% of patients had concomitant diseases or conditions. None of the patients were

Discussion

Both onset of action and duration of action are receiving greater attention as new PDE5 inhibitors are being introduced as alternative treatments for ED. Currently, initial pharmacological treatment for ED involves the use of an oral PDE5 inhibitor [8]. Sildenafil was the first PDE5 inhibitor to become widely available for clinical use [9], and vardenafil and tadalafil, two newer PDE5 inhibitors, were recently approved for this indication in many countries across Europe and the United States [3]

Acknowledgements

This study was partially supported by an independent investigator initiated grant from Pfizer Inc.

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