-
Expert Opinion on Pharmacotherapy Feb 2014Erectile dysfunction (ED) affects over 150 million men worldwide. Oral phosphodiesterase-5 (PDE5) inhibitors are currently used as a first-line therapy and a second-line... (Review)
Review
INTRODUCTION
Erectile dysfunction (ED) affects over 150 million men worldwide. Oral phosphodiesterase-5 (PDE5) inhibitors are currently used as a first-line therapy and a second-line therapy with either intracavernosal (Caverject) or intraurethral (MUSE) alprostadil is required for a few men who show poor response or intolerance to PDE5 inhibitors.
AREAS COVERED
This article reviews the pharmacology, pharmacokinetics, medical applications, efficacy and safety of alprostadil in the treatment of men with ED. The goal of this article is to review the currently published clinical data of alprostadil to establish its potential role in managing men, in particular, those who fail to respond to traditional PDE5 inhibitors. Relevant articles and abstracts were reviewed from PUBMED and conference proceedings.
EXPERT OPINION
Alprostadil, a synthetic form of prostaglandin E1, is used as second-line therapy in managing men with ED. It has a unique role in men with ED secondary to diabetes and ED secondary to radical pelvic surgery (e.g., radical prostatectomy). In view of these new indications, the role of alprostadil is being redefined. Both intracavernosal and intraurethral alprostadil are approved for use in all countries, and following positive results from recent Phase III trials, topical alprostadil has gained approval in Canada.
Topics: Alprostadil; Drug Therapy, Combination; Erectile Dysfunction; Humans; Male; Phosphodiesterase 5 Inhibitors
PubMed: 24369066
DOI: 10.1517/14656566.2014.873789 -
The Annals of Pharmacotherapy 2006To review the pharmacology, pharmacokinetics, efficacy, and safety of topical alprostadil in the treatment of female sexual arousal disorder (FSAD). (Review)
Review
OBJECTIVE
To review the pharmacology, pharmacokinetics, efficacy, and safety of topical alprostadil in the treatment of female sexual arousal disorder (FSAD).
DATA SOURCES
A literature search was conducted using MEDLINE (1966-May 2006), EMBASE, and International Pharmaceutical Abstracts with the search terms alprostadil, female, and sexual dysfunction/drug therapy.
STUDY SELECTION AND DATA EXTRACTION
All published and unpublished clinical trials and abstracts involving the efficacy and safety of topical alprostadil use in women were reviewed. Data on file with the manufacturer were also included.
DATA SYNTHESIS
Topical alprostadil is a vasodilatory agent under development for the treatment of FSAD. In-clinic application of alprostadil increases genital vasocongestion, vaginal erythema, transudates, and some patient-assessed indices of sexual arousal; however, these effects have not been consistently superior to placebo. Three of 4 trials investigating at-home use of topical alprostadil have demonstrated improvements in achievement of satisfactory levels of sexual arousal and successful sexual encounters in patients with FSAD. Adverse events appear to be mild and localized and consist of burning and itching at the application site.
CONCLUSIONS
Two formulations of topical alprostadil are in Phase II clinical trials for the treatment of FSAD. Initial results of clinical trials have demonstrated some beneficial effects on arousal success rates and other subjective measures of sexual arousal; however, these results have been inconsistent and not reproducible in all trials. The results of ongoing clinical studies are needed to further define the role of topical alprostadil in the treatment of FSAD.
Topics: Administration, Topical; Alprostadil; Clinical Trials as Topic; Female; Humans; Sexual Dysfunctions, Psychological; Vasodilator Agents
PubMed: 16757679
DOI: 10.1345/aph.1G472 -
Drug and Therapeutics Bulletin Aug 1995
Comparative Study Review
Topics: Adult; Aged; Alprostadil; Erectile Dysfunction; Humans; Male; Middle Aged
PubMed: 8529540
DOI: 10.1136/dtb.1995.33861 -
American Journal of Therapeutics 1997
Review
Topics: Alprostadil; Arterial Occlusive Diseases; Blood Coagulation; Humans; Neovascularization, Physiologic; Peripheral Vascular Diseases; Platelet Aggregation; Receptors, LDL
PubMed: 10423631
DOI: No ID Found -
DICP : the Annals of Pharmacotherapy Apr 1991
-
Drugs & Aging Jan 1996Intracavernous alprostadil (synthetic prostaglandin E1) is a vasodilating agent which acts by relaxing the smooth muscles of the corpus cavernosum and by increasing the... (Review)
Review
Intracavernous alprostadil (synthetic prostaglandin E1) is a vasodilating agent which acts by relaxing the smooth muscles of the corpus cavernosum and by increasing the diameter of cavernous arteries; this leads to erection. Following intracavernous administration, alprostadil is either locally metabolised or rapidly cleared from the penis into the systemic circulation where it is extensively metabolised by the lungs. Studies suggest that long term use of intracavernous alprostadil may increase penile blood flow, although the clinical relevance of this is not currently known. In men with erectile dysfunction (ED), short term trials have shown that intracavernous alprostadil is superior or equal, in inducing erections, to other intracavernous agents such as papaverine, the combination of papaverine plus phentolamine, linsidomine and topical nitroglycerin (glyceryl trinitrate). Intracavernous alprostadil induced erections in around 70% of patients with ED of various origins in short term studies. 49 to 84% of patients accept the offer of joining self-injection programmes and 13 to 60% of these patients withdraw from such programmes for a variety of reasons. At therapeutic doses, intracavernous alprostadil is well tolerated. The most common adverse event of transient penile pain occurred in around one-third of patients and in 11% of injections, causing 3 to 5% of patients to withdraw from self-injection programmes. Potentially serious adverse events such as priapism and fibrosis occurred in 4 and 8% of patients. Overall, available data suggest that the efficacy of intracavernous alprostadil is superior or equal to that of other erectogenic agents which are in use. Furthermore, the drug is well tolerated especially with regard to serious adverse events. Thus, although further research is necessary to confirm its use in combination with other agents, alprostadil appears likely to become the intracavernous agent of choice for the management of erectile dysfunction.
Topics: Alprostadil; Erectile Dysfunction; Humans; Male; Reaction Time
PubMed: 8785470
DOI: 10.2165/00002512-199608010-00009 -
Expert Opinion on Pharmacotherapy Mar 2004Erectile dysfunction (ED) has serious negative consequences on both sexual experience and emotional well being and affects a broad range of age groups. The prevalence of... (Review)
Review
Erectile dysfunction (ED) has serious negative consequences on both sexual experience and emotional well being and affects a broad range of age groups. The prevalence of ED is associated with increasing age and has been reported to be as high as 70%. Although the disorder is common and underdiagnosed, its treatment can significantly improve patients' quality of life. Systemic treatment with oral phosphodiesterase type-5 (PDE-5) inhibitors is the current standard of care for patients with ED. Some patients, however, have absolute contraindications for PDE-5 inhibitors. In addition, these agents can be associated with adverse effects. Furthermore, because PDE-5 inhibitors are not as effective in patients who have undergone radical prostatectomy or who have severe vascular disease, a substantial unmet medical need exists among patients who have ED as a result of these conditions. Consequently, PDE-5 inhibitor therapy is associated with a high rate of discontinuation, as are intracavernosal or transurethral therapies, which are inconvenient and invasive. Several studies, including four double-blind, placebo-controlled, Phase II trials, show that alprostadil topical cream is efficacious and well-tolerated in ED in patients with mild-to-severe symptoms, in those undergoing treatment for cardiovascular diseases and diabetes and in otherwise healthy ED patients. Thus, alprostadil topical cream is a potential first-choice alternative for ED in patients who do not respond or who cannot tolerate or do not accept PDE-5 inhibitor therapy.
Topics: 3',5'-Cyclic-GMP Phosphodiesterases; Administration, Cutaneous; Alprostadil; Clinical Trials as Topic; Contraindications; Cyclic Nucleotide Phosphodiesterases, Type 5; Erectile Dysfunction; Humans; Male; Phosphodiesterase Inhibitors; Phosphoric Diester Hydrolases; Receptors, Prostaglandin E; Receptors, Prostaglandin E, EP1 Subtype; Treatment Outcome
PubMed: 15013930
DOI: 10.1517/14656566.5.3.623 -
Revue de L'infirmiere Dec 2009
Topics: Alprostadil; Humans; Injections; Male; Muscle Relaxation; Platelet Aggregation Inhibitors; Priapism; Vasodilator Agents
PubMed: 20085033
DOI: No ID Found -
Cellular and Molecular Biology... Aug 2022The study aimed to explore the roles of alprostadil combined with edaravone in inflammation, oxidative stress and Pulmonary function in patients with traumatic...
The study aimed to explore the roles of alprostadil combined with edaravone in inflammation, oxidative stress and Pulmonary function in patients with traumatic hemorrhagic shock (HS). 80 patients with traumatic HS treated in Feicheng Hospital Affiliated to Shandong First Medical University and Tai'an City Central Hospital from January 2018 to January 2022 were enrolled and divided into observation group (n=40) and control group (n=40) according to the randomized control method. Patients in the control group were given alprostadil alone (5 g alprostadil + 10 mL normal saline) in addition to conventional treatment, while those in the observation group received edaravone (30 mg edaravone + 250 mL normal saline) on the basis of treatment in the control group. The patients in both groups were treated via intravenous infusion once a day for 5 days. 24 hours (h) after resuscitation, venous blood were collected to detect serum biochemical indicators such as blood urea nitrogen (BUN), aspartate aminotransferase (AST) and alanine aminotransferase (ALT). Enzyme-linked immunosorbent assay (ELISA) was conducted to determine serum inflammatory factors. Lung lavage fluid was collected to examine pulmonaryfunction indicators such as myeloperoxidase (MPO) and matrix metalloproteinase-9 (MMP-9) activity and to observe the oxygenation index (OI). Blood pressure was measured at admission and 24 h after surgery. The observation group had significantly lowered serum BUN, AST and ALT (p<0.05), the content of serum interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-α) as well as oxidative stress indexes like superoxide dismutase (SOD) and malondialdehyde (MDA) (p<0.05) and pulmonary function indicators (p<0.05) but overtly increased content of SOD and OI. Furthermore, the blood pressure in the observation group dropped to 30 mmHg at admission and rose to the normal range. Alprostadil combined with edaravone effectively reduces inflammatory factors and improves oxidative stress and pulmonary function in patients with traumatic HS, whose efficacy is significantly better than that of alprostadil alone.
Topics: Humans; Shock, Hemorrhagic; Edaravone; Alprostadil; Saline Solution; Hemorrhage; Inflammation; Superoxide Dismutase; Oxidative Stress
PubMed: 36800822
DOI: 10.14715/cmb/2022.68.8.22 -
Drugs 2007Limaprost, an alprostadil (prostaglandin E1) analogue, is a vasodilator that increases blood flow and inhibits platelet aggregation. The efficacy of oral limaprost was... (Review)
Review
Limaprost, an alprostadil (prostaglandin E1) analogue, is a vasodilator that increases blood flow and inhibits platelet aggregation. The efficacy of oral limaprost was evaluated in adult Japanese patients in three randomised, double-blind, 6-week trials. One study included patients with thromboangiitis obliterans and two trials included patients with lumbar spinal canal stenosis. Limaprost was generally well tolerated and serious adverse events were uncommon. THROMBOANGIITIS OBLITERANS: In a randomised, double-blind trial in Japanese patients primarily with thromboangiitis obliterans (n=136), there was no significant difference between patients receiving limaprost 30 microg/day and those receiving oral ticlopidine 500 microg/day in the improvement of ischaemic symptoms. LUMBAR SPINAL CANAL STENOSIS: Limaprost 15 microg/day was superior to limaprost 3 microg/day for overall drug usefulness and overall improvement from baseline to study end in a phase III trial in 146 patients with lumbar spinal canal stenosis. Assessment of overall improvement considered various objective symptoms (e.g. muscle strength, walking ability) and subjective symptoms (e.g. pain or numbness in extremities), while overall usefulness also considered safety issues. The efficacy of limaprost 15 microg/day was not significantly different from that of 30 microg/day, but tended to be better than that of 6 microg/day in a phase II trial in patients with lumbar spinal canal stenosis and normal straight leg raise test results. The optimal dosage of limaprost for this indication was therefore deemed to be 15 microg/day.
Topics: Alprostadil; Animals; Clinical Trials as Topic; Humans; Lumbar Vertebrae; Platelet Aggregation Inhibitors; Spinal Stenosis; Thromboangiitis Obliterans; Vasodilator Agents
PubMed: 17209669
DOI: 10.2165/00003495-200767010-00010