Recent advancement in diagnosis of vasculogenic impotence.
(1/63)
Several dynamic tests with vasoactive drugs are available for evaluating penile vascular inflows and outflows, ranging from simple pharmacologic test to more invasive radiologic sets. However, there is still no perfect single test to reflect the penile vascular flow. All possible efforts should be exerted to get the greatest erectile effect to avoid an underestimation of blood flow to the corpora due to incomplete relaxation of the trabecular smooth muscle. Appreciation of the type and frequency of anatomical variations and potential collateral routes is important in interpreting penile arterograms and in evaluating the hemodynamic significance of suspected arterial disease. Choice of the vascular tests should always depend on the purpose of testing. (+info)
Are normal hemodynamic responses invariably associated with normal penile rigidity and potency?
(2/63)
The existence and importance of patients with low penile buckling pressure and normal penile hemodynamic status have been recently recognized. We assessed the ratio of inadequate erection for vaginal penetration (low buckling pressure) in patients with normal penile vascular system proved with penile Doppler ultrasonography. A total of 101 patients with normal penile vascular status were retrospectively scrutinized dependent on penile axial rigidity (buckling pressure). Ninety patients had sufficient penile axial rigidity (> or = 550 g) whereas in the remaining 11 patients (11%) inadequate penile buckling pressure for vaginal penetration (< 550 g) was determined. Penile geometric and mechanical properties should not be overlooked during the evaluation of penile vascular system lest the patient be incorrectly diagnosed as having psychogenic impotence. (+info)
Hair analysis for pharmaceutical drugs. II. Effective extraction and determination of sildenafil (Viagra) and its N-desmethyl metabolite in rat and human hair by GC-MS.
(3/63)
In order to study the incorporation of sildenafil (SDF) and its N-demethylated metabolite (norSDF) into hair, animal model experiments were carried out. After shaving the back hair, SDF was dosed to two sets of three male dark-agouti pigmented rats (5 weeks old) per each group at 25 mg/kg once a day for 5 successive days with intraperitoneal (i.p.) (set1) and oral administration (set2). The regrown back hair was collected 14 d after the first administration. Three typical extraction methods, using methanol-5 M hydrochloric acid, methanol-trifluoroacetic acid and 1 M sodium hydroxide, were evaluated using the rat hair samples containing SDF and norSDF. Methanol-5 M hydrochloric acid was the best extraction method in terms of high efficiency and reproducibility. The extract was purified using Bond Elut Certify columns and was derivatized with trimethylsilylimidazole: N,O-bis(trimethylsilyltrifluoroacetamide): trimethylchlorosilane (3: 3: 2) at 90 degrees C for 30 min. The trimethylsilylated products were analyzed by GC-MS using selected ion monitoring. SDF and norSDF were simultaneously detected in the rat hair. The hair concentrations were 4.9-6.3 (av. 5.8) ng/mg and 15.6-20.3 (av. 17.6) ng/mg for SDF and norSDF, respectively, with i.p. administration, and 2.6-4.1 (av. 3.6) ng/mg and 8.1-10.4 (av. 9.1) ng/mg with oral administration. The hair concentrations of norSDF were about three times higher than those of SDF, and the ratios of both compounds showed no significant difference between i.p. and oral administrations. This method was applied to the scalp hair of two patients who orally took SDF at regular intervals for the treatment of penile erectile dysfunction. The hair concentrations of SDF and norSDF in the two patients were 19.8 and 55.9 ng/mg, and 1.7 and 5.6 ng/mg, respectively. (+info)
Is there a common pathophysiology of erectile dysfunction and how does this relate to new pharmacotherapies?
(4/63)
Many basic and clinical studies show erectile dysfunction (ED) to be caused by a wide variety of factors. Although these factors can be divided into psychological and organic origins and these too can further be subdivided, many patients will show complex patterns of causes for ED ('mixed ED'). Many of these factors will have a direct or indirect impact on the efficacy of centrally and peripherally acting drugs, thus necessitating a variety of drugs with different modes of action and different modes of application to ensure appropriate therapy for many patients. However, some factors will render all imaginable forms of pharmacological options totally inefficient, thus necessitating forms of treatment other than pharmacotherapy. (+info)
A population pharmacokinetic analysis of sildenafil citrate in patients with erectile dysfunction.
(5/63)
AIMS: To analyse the pharmacokinetics of sildenafil citrate in patients with erectile dysfunction in order to characterize covariate relationships and assist in the development of rational dosage strategies. METHODS: A population pharmacokinetic sampling strategy was incorporated into five phase III clinical study protocols. Overall, 2077 patients, 1335 of whom received sildenafil, were asked to take an additional dose of study drug before their scheduled clinic visits on four or five occasions throughout the study duration. A single plasma sample was obtained at random times postdose (range 1--7 h), and a total of 4582 samples were assayed (average 3.4 samples per individual). RESULTS: For the population average patient (age 58 years; aspartate transaminase [AST], 24 IU l(-1); weight, 87 kg; not receiving CYP3A4 potential inhibitors), typical values for sildenafil (mean +/- SE) were 58.5 +/- 1.4 l h(-1) for apparent clearance (CL/F), 310 +/- 6.92 l for volume of distribution (V/F), and 2.6 +/- 0.176 h(-1) for first-order absorption constant (ka). The value for ka is associated with meal consumption within 2 h predose, at all other times ka was equivalent to an instantaneous bolus administration. The interindividual variabilities were 29% for CL/F, 20% for V/F, and 210% for ka. Over a dose range of 25--100 mg sildenafil, the pharmacokinetics exhibited dose proportionality. There was evidence of nonproportionality (40% increase on average) in relative bioavailability with respect to the 200-mg dose (P<0.001) relative to the other doses. Age, AST concentration, and co-administration with CYP3A4 potential inhibitors significantly influenced CL/F of sildenafil (P<0.001, for each relationship). For age and AST, the extent of the linear relationships (extrapolated from population average values) included a 4% decrease in CL/F for every decade increase and a 6% decrease in CL/F for every 10-unit increase, respectively. Following co-administration of CYP3A4 potential inhibitors, a 14% decrease in CL/F was estimated. Only body weight was found to significantly (P<0.001) influence V/F (a 6% increase in V/F for every 10-kg increase). CONCLUSIONS: The pharmacokinetics of, and covariate influences on, sildenafil in patients with erectile dysfunction were shown to be consistent with those demonstrated in phase I volunteer studies. (+info)
Onset and duration of action of sildenafil for the treatment of erectile dysfunction.
(6/63)
AIMS: To determine the onset and duration of action of sildenafil in patients with erectile dysfunction (ED). METHODS: Two randomised, double-blind, placebo-controlled, two-way crossover studies were conducted in men with ED of no known organic cause. Study I: The time to onset of erections after sildenafil (50 mg) or placebo dosing following visual sexual stimulation (VSS) was assessed in 17 patients. Patients not achieving >60% penile rigidity by 70 min postdose as measured by a RigiScan(R) monitoring device were assigned an onset time of 70 min. Study II: The duration of grade 3 (hard enough for penetration) and grade 4 (fully hard) erections, determined by self-assessment during 60 min of VSS starting 2 and 4 h after sildenafil (100 mg) or placebo dosing, was measured in 16 patients. RESULTS: Study I: The median time (range) to onset of erections was 27 min (in a range of 12--70) after receiving sildenafil 50 mg. In the sildenafil group, 71% of patients experienced onset of erections within 30 min of dosing, and 82% responded within 45 min. Of the patients who achieved >60% penile rigidity after sildenafil, 86% had done so by 30 min after dosing. Study II: When VSS began 2 h postdose, the median duration of grade 3 or 4 erections was 19.5 min (0--55) for sildenafil vs 0 min (0--23) for placebo. When VSS began 4 h postdose, the median duration was 5 min (0--45) for sildenafil compared with 0 min for placebo (0--27). CONCLUSIONS: Sildenafil is an effective oral treatment for ED that produces a penetrative erection as early as 12 min and for most patients, within 30 min after dosing, and a duration of action lasting at least 4 h. (+info)
Role of penile vascular insufficiency in erectile dysfunction in renal transplant recipients.
(7/63)
The objectives of this study were to define the role and haemodynamic features of penile vascular insufficiency in impotent renal transplant recipients (RTR) as well as to establish the possible vascular risk factors for impotence in these patients. A total of 54 RTR (35 impotent and 19 potent) and 21 potent healthy subjects were included in this study. All patients were assessed clinically and by measurement of serum creatinine, serum bilirubin, cyclosporine blood levels, haemoglobin and total serum cholesterol. All subjects were subjected to intracavernous injection of 20 microg prostaglandin E1 followed by colour Duplex sonographic examination. Our results showed that impotent RTR were significantly more likely than potent RTR to have hypertension, diabetes and hypercholesterolaemia (P<0.05). Arterial occlusive disease was identified in 42.9% of impotent RTR. Findings suggestive of veno-occlusive dysfunction were found in 68.6% and 26.3% of impotent and potent RTR, respectively (P=0.003). Unilateral ligation of the internal iliac artery has a negative role on haemodynamic parameters compared to unilateral end-to-side anastomosis to external iliac artery in impotent RTR (P<0.05). Impotent RTR receiving more than one antihypertensive drug showed significant decrease in basal peak systolic velocity (PSV), dynamic PSV, erectile angle and cavernosal artery diameter compared to those receiving one drug (P<0.05). In conclusion, penile vascular insufficiency appears to play a substantial role in the pathogenesis of impotence in transplant patients. Anastomosis of the graft to external iliac artery could preserve the potency to some degree. Antihypertensives should be reduced as much as possible to avoid their negative effects on erectile function. (+info)
Erectile dysfunction and the cardiovascular patient: endothelial dysfunction is the common denominator.
(8/63)
Erectile dysfunction (ED) is a common condition and studies predict that it will become even more common in the future. There is increasing evidence to suggest that it is predominantly a vascular disease and may even be a marker for occult cardiovascular disease. The common pathological process is at the level of the endothelium, and cardiovascular risk factor control may be the key to preventing ED. Many men with established cardiovascular disease have ED. Specific guidelines for the management of ED in these patients have been produced by an expert panel. Cardiovascular risk stratification is an important initial step in managing such patients. In cardiac patients considered to have low cardiovascular risk, the management of ED can be safe and effective. (+info)