الفهرس 
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Abstract
(ED) is defined as “the consistent inability of the male to achieve and/or maintain a penile erection firm enough for satisfactory sexual coitus” (NIH, 1993).ED is common throughout the world, increases in prevalence with aging. It is a problem that always affects both partners and over 87% of men with ED and almost 60% of affected couples regard the disorder as a limitation to their quality of life (Sommer and Engelmann, 2004).
Treatment of ED includes psychosexual/relationship therapy, oral pharmacotherapy, external devices and Penile prosthesis (Hatzimouratidis et al., 2010). For many ED patients the ideal therapy is the oral medication which is rapidly acting, effective, simple to use and safe (Carson, 2000).
Sildenafil is the first safe and effective oral ED medication. It acts by inhibiting PDE-5, thus promoting erection by inhibiting degradation of cGMP, a chemical messenger whose production leads to smooth muscle relaxation and, in the case of penile vascular smooth muscle, leads to erection. Sildenafil efficacy is dose-related and ranging between 56% and 89% (Raina et al., 2005). Additionally, oral administration of sildenafil is accompanied by dose-responsive undesirable side effects (Pfizer labs, 2010).
Apomorphine is one of the agents that can be used sublingually as ED therapy. It acts as a dopamine receptor (D1/D2) agonist that initiates and enhances the erectile response to pro-erectile stimuli through a unique central action. As Apomorphine is less effective than sildenafil as erectogenic, if used alone, it needs to be used at higher doses to give a satisfactoryerectogenic effect. This unfortunately carries the risk of high dose-related side effects, mainly nausea (Afif-Abdo et al., 2008).Though apomorphine is less effective than sildenafil, it doesn’t suffer from some sildenafil contraindications, like co-administration with nitrates (Sommer and Engelmann, 2004).
A singletherapeutic agent may not be ideal for sustainingpenile rigidity, especially when comorbidities andthe severity of erectile dysfunction are taken intoaccount, so researchers focus on developing new combination therapies (Sommer and Engelmann, 2004).
The aim of this study was to evaluate the efficacy and tolerability of sildenafil + apomorphine SL combination in one dosage unitcompared to sildenafil SL in men with ED of various etiologies and severities.
This was a prospective randomized crossover single-blind study conducted on 50 male patients (mean age 49.1 years, SD 8.9) with ED of various etiologies and severities recruited from “Dr. Khaled Salem private clinic” on an outpatient basis.
Patients were subjected to history-taking and physical examination during the 1-week screening phase at the beginning of the study to check for eligibility. During the 10-week treatment phase, eligible patients were randomized to start on Treatment (A) (Sildenafil citrate 50 mg SL tablets) or Treatment (B) (Sildenafil citrate 50 mg and Apomorphine 3 mg SL tablets).The sequence of the 2 treatments was determined by a randomization list in blocks in closed packets. Patients started on their randomly allocated treatment arm and continued for 4-week period, followed by a washout period of 2-week, after which the patient changed to the alternate treatment for an additional 4-week period.
Eachpatient received a study-specific home-use event diary and was asked to use it to record his experience within 12 hours after each sexual attempt. At the end of each intervention, patients were assessed using their responses to the event diary, (IIEF-5) scorecompared to baseline, SEP diary (Question 2 and 3) and GAQs.
The primary efficacy end point was the percent of attempts resulting in erection firm enough for intercourse. Secondary endpoints included the percent of attempts resulting in successful intercourse,change in the IIEF-5 score compared to baseline, response to SEP diary (question 2 and 3), GAQs and finally patient preference, measured at the end of the study.
Analysis of tolerability endpoint included the adverse events and the palatability complaint; such information was obtained during office visits from patient diaries and comments by the patient.Only 43 patients completed the whole schedule. None of the 7 exclusions could be explained because of side effects of the drugs.
Combination was significantly superior to sildenafil according to all the measurableendpoints.The primary efficacy endpoint, the percent of attempts resulting in erection firm enough for intercourse, was significantly higher with sildenafil + apomorphine combination than with Sildenafil (77.6% and 63.1% respectively, p <0.001). The percent of attempts resulting in successful intercourse was significantly higher with sildenafil + apomorphine combination than with Sildenafil (51.1% and 34% respectively, p <0.001). The change in the median IIEF-5 score from baseline was significantly greater with sildenafil + apomorphine combination than with sildenafil (18 and 15 respectively with baseline of 7, P<0.001). The proportion of men answering‘yes’ to question 2of the SEP diarywas55.8% for sildenafil and 79.1% for sildenafil + apomorphine combination (P<0.01),‘Yes’ to question 3of the SEP diarywas44.2% for sildenafil and 65.1% for sildenafil + apomorphine combination (P<0.05),‘Yes’ to question 1 of the GAQswas74.4% for sildenafil and 95.3% sildenafil + apomorphine for combination (P<0.01), and ‘Yes’ to question 2 of the GAQswas72.1% for sildenafil and 93.0% for sildenafil + apomorphine combination (P<0.01). Finally, at the end of the study, when patients were asked which treatment they preferred, 88.4% selected sildenafil + apomorphine combination, 4.6% preferred sildenafil intervention, and the remaining7%liked both interventions equally.
Overall adverse events were mild or moderate and did not require treatment interruption. There was no significant difference in the incidence of adverse events between sildenafil + apomorphine combination and sildenafil alone (P=1.000). Palatability complaint was not clinically significant after both interventions. Also, there was no significant statistical difference between the two interventions regarding the reported palatability complaint (P=1.000).