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Biomedical subjects

V A Place

Publications and source records attributed to V A Place.

At least 19 recordsLinked to original sources
PubMed1998

Efficacy and safety of transurethral alprostadil therapy in men with erectile dysfunction. MUSE Study Group.

OBJECTIVE: To examine the safety and efficacy of transurethral pharmacotherapy for erectile dysfunction, involving the use of a novel therapeutic system to administer alprostadil (prostaglandin E1) to the urethral mucosa in a double-blind, randomized, parallel, placebo-controlled study conducted in five countries in Europe. PATIENTS AND METHODS: In an outpatient setting, patients with primarily organic erectile dysfunction of at least 3 months' duration were treated with transurethral alprostadil, in an open-label, dose-escalating study. Testing stopped when the dose provided an erection sufficient for intercourse, as assessed by the patient and the investigator. Patients who achieved a sufficient response were then randomized to either active medication at the selected dose or to placebo for use at home for 3 months. After each home administration, patients recorded in diaries whether or not sexual intercourse occurred and any adverse reactions to the drug. RESULTS: A total of 249 patients were treated in an outpatient setting; of these patients, 159 (64%) achieved an erection sufficient for intercourse and were randomized (1:1) to either active medication or placebo for home treatment. Of the patients randomized to alprostadil for home treatment, 69% reported intercourse at least once, compared with 11% of patients randomized to placebo (P < 0.001). The most common adverse reaction, urethral pain/burning, was reported by 7% of patients in the clinic. Most patients (83%) graded transurethral alprostadil as causing minimal or no discomfort in the clinic. No patient reported priapism or developed penile fibrosis. CONCLUSION: Alprostadil delivered transurethrally by this system was well tolerated and effective in treating erectile dysfunction.

Adult↗
PubMed1998

The effect of transurethral alprostadil on the quality of life of men with erectile dysfunction, and their partners. MUSE Study Group.

OBJECTIVE: To evaluate the impact of treatment for erectile dysfunction on the quality of life of men and their partners. PATIENTS AND METHODS: The study included 249 men with organic erectile dysfunction of more than 3 months' duration who self-administered transurethral alprostadil in an open-label, dose-escalating manner in an outpatient medical setting. Patients with a sufficient response (159) were randomly assigned in a double-blind protocol to either active medication or placebo for 3 months at home. Patients and partners each completed quality-of-life questionnaires before and after treatment. RESULTS: In the clinic 159 of the 249 men (64%) had an erection sufficient for intercourse when using transurethral alprostadil. At home, 46 of 67 men (69%) reported intercourse at least once on transurethral alprostadil, compared with eight of 73 (11%) on placebo (P < 0.001). Patients on alprostadil showed a 34% improvement in their 'relationship with partner', a 5% improvement in 'personal wellness', and a 71% improvement in 'quality of erection' domains, compared with a decline of 11%, 8% and 1%, respectively, in patients on placebo (P < 0.005 for each comparison). Partners of patients on alprostadil showed a 35% improvement in the 'relationship with partner' domain, compared with a 12% improvement in the placebo group (P = 0.028). There was a trend toward improvement in other partner domains. Urogenital pain was reported by 14% of patients during home treatment. CONCLUSION: The resumption of sexual intercourse with the use of transurethral alprostadil was accompanied by an improvement in several important quality-of-life domains in patients and their partners.

Adult↗
PubMed1998

Erectile response to transurethral alprostadil, prazosin and alprostadil-prazosin combinations.

PURPOSE: Transurethral alprostadil has been shown to be efficacious in many men with erectile dysfunction. We compared transurethral alprostadil and prazosin alone, and in combination to treat this disorder. MATERIALS AND METHODS: In this double-blind, placebo controlled study the erectile responses to transurethral alprostadil, prazosin and alprostadil-prazosin combinations were assessed in 234 men 26.8 to 81.5 years old with complete organic erectile dysfunction. Patients self-administered a random sequence of 7 doses in the clinic in 4 weeks. The erectile response was assessed using categorical and visual analog scales. RESULTS: Full penile enlargement or rigidity was achieved by 165 of the 234 men (70.5%) after at least 1 active dose of medication. The most effective alprostadil dose (500 microg.) resulted in full penile enlargement or rigidity in 51.8% of administrations, whereas the most effective prazosin dose (2,000 microg.) and placebo resulted in a similar response in 12.7 and 2.7%, respectively (p <0.001). The 500/2,000 microg. alprostadil/prazosin combination, which resulted in full enlargement or rigidity in 58.9% of doses, was only slightly better than the most effective dose of alprostadil alone (500 microg.). However, combinations of 125/500 and 250/500 microg. alprostadil/prazosin were more effective (p <0.01) than 125 and 250 microg. alprostadil given alone, respectively. The most common side effect of therapy was penile pain, which rarely led to study discontinuation. Hypotension most commonly developed at the higher alprostadil-prazosin combination. CONCLUSIONS: Transurethral alprostadil and alprostadil-prazosin combinations produced erections in men with complete organic erectile dysfunction. This combination therapy may be an option in patients who do not respond to transurethral alprostadil alone.

Adrenergic alpha-Antagonists↗
PubMed1997

Treatment of men with erectile dysfunction with transurethral alprostadil. Medicated Urethral System for Erection (MUSE) Study Group.

BACKGROUND: Erectile dysfunction in men is common. We evaluated a system by which alprostadil (prostaglandin E1) is delivered transurethrally to treat this disorder. METHODS: Alprostadil was delivered transurethrally in a double-blind, placebo-controlled study of 1511 men, 27 to 88 years of age, who had chronic erectile dysfunction from various organic causes. The men were first tested in the clinic with up to four doses of the drug (125, 250, 500, and 1000 microg); those who had sufficient responses were randomly assigned to treatment with either the effective dose of alprostadil or placebo for three months at home. RESULTS: During in-clinic testing, 996 men (65.9 percent) had erections sufficient for intercourse. Of these men, 961 reported the results of at least one home treatment; 299 of the 461 treated with alprostadil (64.9 percent) had intercourse successfully at least once, as compared with 93 of the 500 who received placebo (18.6 percent, P<0.001). On average, 7 of 10 alprostadil administrations were followed by intercourse in men responsive to treatment. The efficacy of alprostadil was similar regardless of age or the cause of erectile dysfunction, including vascular disease, diabetes, surgery, and trauma (P<0.001 for all comparisons with placebo). The most common side effect was mild penile pain, which occurred after 10.8 percent of alprostadil treatments, but the pain rarely resulted in refusal to continue in the study. Hypotension occurred in the clinic in 3.3 percent of men receiving alprostadil. Hypotension-related symptoms were uncommon at home. No men had priapism or penile fibrosis. CONCLUSIONS: In men with erectile dysfunction, transurethral alprostadil therapy resulted in erections in the clinic and in intercourse at home.

Adult↗
PubMed1996

A double-blind, placebo-controlled evaluation of the erectile response to transurethral alprostadil.

OBJECTIVES: Previous studies have indicated that the urethra may provide an effective route for administering vasoactive medication for the treatment of erectile dysfunction. We evaluated the safety and efficacy of alprostadil administered intraurethrally at home for the treatment of this disorder. METHODS: This prospective, multicenter, double-blind, placebo-controlled study evaluated the erectile response to randomly assigned doses of transurethral alprostadil at home in 68 men with long-standing (mean 41 months) erectile dysfunction of primarily organic etiology. Patients completing the study each administered a random sequence of four different doses (125, 250, 500, and 1000 micrograms) and placebo over a 2 to 4-week period. Assessments included the couples' ability to have intercourse, patient ratings of erectile response by both categorical and visual analogue scales, penile volume measurements, and overall assessments of comfort and ease of administration. RESULTS: Overall, 75.4% (49 of 65) of study patients achieved full enlargement of the penis and 49.2% (32 of 65) achieved an erection judged by the patient to be sufficient for intercourse. In addition, 63.6% (42 of 66) of patients reported intercourse. Efficacy was similar across etiologies. The most common side effect was penile pain, which occurred in association with 9.1% to 18.3% of alprostadil administrations, depending on dose. Mean comfort ratings ranged from 79 to 87, depending on dose, where 0 = severe discomfort and 100 = comfortable; ease of administration scores were above 90 for each dose, where 0 = difficult and 100 = easy. There were no episodes of priapism in this study. CONCLUSIONS: Short-term treatment with transurethral alprostadil produced erections resulting in sexual intercourse in most patients with chronic erectile dysfunction. This therapy may be a useful treatment option for patients with erectile dysfunction.

Adult↗
PubMed1988

Substitution therapy of hypogonadal men with transdermal testosterone over one year.

Current testosterone substitution therapy either by injectable or oral testosterone esters suffers from markedly fluctuating serum testosterone levels often far above or below the physiological range. Recently, a transdermal therapeutic system (TTS) for the delivery of testosterone was developed which, when applied to the scrotum, provides smooth serum testosterone levels. Here we report results from seven hypogonadal men treated with the TTS for 14 months by applying a new patch every day. In all patients serum testosterone and dihydrotestosterone (DHT) determined 3-5 h after applying a new patch increased significantly and remained within the physiological range during the entire treatment period. The DHT/testosterone ratio remained constant. In 4 of these patients and 2 others under TTS treatment serum testosterone and DHT were also determined over a 24-h period at regular intervals. In these patients serum testosterone levels in the physiological range were seen during the entire observation period, whereas an increase in the DHT/testosterone ratio occurred towards the end of the one-day treatment phase. All patients in the 14-month treatment study were clinically well substituted and responded with good compliance. Clinical chemistry showed no abnormalities during treatment. Thus, the TTS appears to be an effective and safe new modality for the treatment of male hypogonadism.

Administration, Cutaneous↗
PubMed1987

Transdermal delivery of testosterone.

We administered testosterone transdermally to six hypogonadal men by applying a thin flexible polymeric membrane containing testosterone to the scrotum. Each man wore a placebo membrane and three doses (5, 10, and 15 mg) of testosterone-containing membranes for 22 h/day. Each dose was worn for 1 week, and one dose was worn a second week. Blood was sampled frequently for one 22 h period on the seventh day of each treatment period. After the application of a membrane, the serum testosterone concentration rose rapidly, reached a peak in 2-3 h, and decreased slowly to 60-80% of the peak value by 22 h. The mean (+/- SE) 22-h average testosterone concentration during the wearing period was dependent on the testosterone content of the membrane (placebo, 135 +/- 38 ng/dl; 5 mg, 348 +/- 66 ng/dl; 10 mg, 455 +/- 77 ng/dl; and 15 mg, 624 +/- 65 ng/dl; P less than 0.001, by analysis of variance). When the same dose was worn twice, the mean coefficient of variation was 13.9%. We conclude that the transdermal application of testosterone to hypogonadal men reproducibly raises their serum testosterone concentrations to within the normal range, and that it, therefore, warrants evaluation as a treatment for male hypogonadism.

Administration, Cutaneous↗
PubMed1985

A double-blind comparative study of Estraderm and Premarin in the amelioration of postmenopausal symptoms.

Patients whose postmenopausal symptoms were being satisfactorily controlled with conjugated equine estrogens, either 0.625 mg/day (n = 57) or 1.25 mg/day (n = 67), participated in a study that compared the efficacy of these oral regimens with that of 17 beta-estradiol, 0.1 mg/day, administered through intact skin. The study was a multicenter, double-blind, randomized, parallel-group trial during which two thirds of the patients who received each dosage of conjugated equine estrogens were changed to an estradiol transdermal system while the remainder continued with conjugated equine estrogens. A total of 124 patients was included in the analysis of efficacy. The analysis revealed no significant differences between the estradiol transdermal system and conjugated equine estrogens in control of hot flushes or other postmenopausal symptoms and no statistically significant differences between treatment groups in regard to estrogen-related side effects. Minor topical reactions to the transdermal systems were reported during only about 20% of study weeks. Thus, transdermal estradiol, 0.1 mg/day, appears to be equally effective as conjugated equine estrogens, 0.625 or 1.25 mg/day, for controlling postmenopausal symptoms and is well tolerated.

Administration, Topical↗
PubMed1985

Pharmacokinetics and pharmacodynamics of transdermal dosage forms of 17 beta-estradiol: comparison with conventional oral estrogens used for hormone replacement.

This open-label, multiple-crossover study compared the pharmacokinetics and pharmacodynamics of transdermal 17 beta-estradiol and two oral forms of estrogen replacement therapy in postmenopausal women. The transdermal systems delivered either 0.025, 0.05, or 0.1 mg/day; oral dosages were 2 mg of micronized 17 beta-estradiol or 1.25 mg of conjugated equine estrogens. Transdermal estradiol provided serum and urinary levels of estradiol conjugates typical of the early follicular phase of the premenopausal woman and an estradiol/estrone ratio that approximated 1. The increments of both serum and urinary estradiol showed dose proportionality. Serum levels of estradiol obtained 24 hours after oral administration of estrogens were in a range similar to the steady-state levels obtained with transdermal estradiol delivery. Oral estrogens, however, induced an excessive rise in estrone to levels far beyond those observed in premenopausal women. Continuous application of transdermal estradiol over 3 weeks did not result in any accumulation of estradiol or estradiol conjugates. After only three doses of oral estrogens, there were signs of retention of estrogens. Suppression of gonadotropins by oral and transdermal administration of estrogens was in a similar range. This observation supports the conclusions that levels of circulating estradiol are relevant to efficacy, and that excessively high levels of estrone after oral administration of estrogens merely represents a nonphysiologic precursor or metabolite pattern.

Administration, Oral↗
PubMed1976

Visual effects of pilocarpine in glaucoma comparative study of administration by eyedrops or by ocular therapeutic systems.

Eighteen glaucoma patients each received four pilocarpine regimens in random sequence: 1% and 4% eyedrops and 20mug/hr and 40mug/hr ocular therapeutic systems. Unimportant changes in refraction, near vision, and distance vision occurred during the use of either ocular therapeutic system. Miosis with ocular therapeutic systems was almost always less intense and variable than with eyedrops. Refractive changes occurred in 12 patients following 1% pilocarpine and in 16 patients following 4% pilocarpine drops; decreased distance vision occurred in nine patients after 1% drops and in 12 patients after 4% drops. Fewer patients showed decreases in near vision. In all cases, visual effects peaked one half hour after eyedrop instillations and returned gradually toward normal in the next two to three hours. Intraocular pressure levels were within comparable ranges during all four treatments, but the ocular therapeutic systems maintained pressure at a more constant level.

Adolescent↗
PubMed1976

Steroid delivery systems for contraception.

Scientific disciplines not normally associated with pharmaceutical development have been employed to enhance the effectiveness and attractiveness of two approaches to steroidal contraception. The use of a bioerodible polymeric carrier for predictable systemic steroidal administration has removed the largest hurdle to the development of a subcutaneous contraceptive implant. A polymeric progesterone delivery system has provided a method for localizing hormonal contraception in the uterine cavity. Extensions of these technologies may provide two useful tools in limiting fertility in an already overcrowded world.

Biocompatible Materials↗
PubMed1975

Comparative pharmacologic effects of pilocarpine administered to normal subjects by eyedrops or by ocular therapeutic systems.

Normal volunteers used 1, 2, and 4% pilocarpine eyedrops, three times daily, or ocular therapeutic systems placed in the conjunctival cul-de-sac to control intraocular pressure. The systems continuously release 20 and 40 mug/hour of pilocarpine for one week. Although the amount of drug delivered to the eye from the ocular therapeutic system was one fifth that obtained from the eyedrops, the decrease of intraocular pressure was comparable. The ocular therapeutic systems produced small, constant effects on visual acuity, refractive error, and miosis that did not cause visual handicaps or require correction. The effects of eyedrops on these visual factors were large and varied and produced marked visual handicaps that were not correctable with spectacles. Despite its comparable hypotensive effect in normal subjects, continuous delivery of pilocarpine by means of an ocular therapeutic system elicits less severe side effects than pilocarpine eyedrops.

Adult↗