BACKGROUND: Vardenafil is a phosphodiesterase type 5 inhibitor, used in erectile dysfunction. This study aimed to evaluate the pharmacokinetics and tolerability of vardenafil following a single oral administration in healthy male subjects. METHODS: A randomized, double-blind, placebo-controlled, single dosing, dose-escalation study was conducted in 30 healthy subjects. A single oral dose of vardenafil or placebo was given to 10 subjects (8 active + 2 placebo) in each dose group of 5, 10 and 20 mg. Serial blood and urine samples were obtained up to 48 hours for pharmacokinetic analysis. Vardenafil and its metabolite were detected by high performance liquid chromatography tandem mass spectrometry assay. RESULTS: A total of 45 adverse events (AE) were reported in 22 subjects, including 5 AEs from placebo treatment, and all the AEs were mild, except one case of moderate nasal stuffiness. Vardenafil was absorbed after a single oral dose, with the tmax of 0.5-1.0 hours. The Cmax and AUClast were 10.21 +/- 3.68 ug/L(mean +/- SD) and 18.08 +/- 7.44 ugxh/L in 5 mg dose group, 19.79 +/- 12.13 ug/L and 38.61 +/- 21.04 ugxh/L in 10 mg dose group and 53.16 +/- 37.01 ug/L and 110.05 +/- 69.65 ugxh/L in 20 mg dose group. Dose-linearity on AUClast and Cmax of vardenafil were observed in three dose groups. In all dose groups, the fraction excreted in urine was less than 1%. CONCLUSION: The vardenafil was tolerable over a single dose range of 5 - 20 mg. The pharmacokinetics of vardenfil after a single oral dose was explored and linear pharmacokinetic characteristics were observed over the dose range of 5 - 20 mg in healthy subjects.
Administration, Oral ; Chromatography, Liquid ; Erectile Dysfunction ; Humans ; Imidazoles ; Male ; Piperazines ; Sulfones ; Tandem Mass Spectrometry ; Triazines

OBJECTIVE: To evaluate erectile dysfunction in patients with spinal cord injury and the relationship between patient's subjective answers and the results of objective tests regarding erectile dysfunction. METHOD: Twenty-one male patients with erectile dysfunction after spinal cord injury were administered with nocturnal penile tumescense and rigidity testing (NPTR) using Rigiscan(R) over 2 consecutive nights. NPTR using Rigiscan(R) at second night was performed after oral administration of sildenafil 50 mg. Answer of the global efficacy question (GEQ) after oral administration of sildenafil 50 mg and the parameters of NPTR were compared. RESULTS: After oral administration of sildenafil 50 mg, number and duration of erectile episodes, and duration of rigidity greater than 60% on NPTR improved significantly (p< 0.05). Sixteen out of seventeen patients (94.1%) who showed improved nocturnal erection after oral administration of sildenafil 50 mg answered that they had an improved erectile function after sildenafil. All four patients (100%) who showed no improvement in nocturnal erection after sildenafil answered that their erectile function was not improved after oral administration of sildenafil 50 mg. CONCLUSION: We expect NPTR using Rigiscan(R) might be useful for the evaluation of erectile dysfunction in men with spinal cord injury.
Administration, Oral ; Erectile Dysfunction ; Humans ; Male ; Piperazines ; Purines ; Spinal Cord ; Spinal Cord Injuries ; Sulfones ; Sildenafil Citrate

AIMTo determine the effect of sildenafil citrate on the nocturnal penile erections (i.e. time to onset, the duration of erection, and the interval between first and second erections) of healthy young men.

METHODSTwenty-two potent men, 23-29 years old, were recruited for the study. All subjects completed three sessions over consecutive nights using the RigiScan monitoring device (Dacomed, Minneapolis, USA). After a first night of adaptation, night 2 records were their baseline values, and on night 3 they received 100 mg of sildenafil citrate. Statistical comparisons were done between the second and third night data.

RESULTSThe mean time to onset of the first erection with sildenafil citrate was (34+/-18) min, whereas it was (74+/-24) min (P 0.0001) without sildenafil citrate. The number of erections observed during the first 5 h after sildenafil citrate medication was 3.6+/-0.5 in contrast to 2.4+/-0.5 with no medication (P=0.001). The interval between first and second erections was shorter with sildenafil citrate: (52+/-26) min vs. (85+/-34) min (P = 0.01). The duration of the last erection was statistically significantly longer with the sildenafil citrate: (64 +/-33) min vs. (42 +/-28) min (P 0.001).

CONCLUSIONHealthy young men achieved erection within 34 min after sildenafil citrate administration, which is shorter than the 1 h interval proposed by the manufacturer. The interval between the first and second erections was shorter and the duration of the last nocturnal erection was longer.

Administration, Oral ; Adult ; Humans ; Male ; Penile Erection ; drug effects ; Piperazines ; administration & dosage ; Purines ; Sildenafil Citrate ; Sulfones ; Time Factors ; Vasodilator Agents ; administration & dosage

Child ; Humans ; Hypertension, Pulmonary ; drug therapy ; Phosphodiesterase Inhibitors ; therapeutic use ; Piperazines ; administration & dosage ; therapeutic use ; Purines ; administration & dosage ; therapeutic use ; Sildenafil Citrate ; Sulfones ; administration & dosage ; therapeutic use

BACKGROUND: The objective of this study was to compare the pharmacokinetics and safety between newly developed sildenafil (Please Orally Soluble Film) and sildenafil citrate (VIAGRA(R)) after single oral administration in healthy Korean male subjects. METHODS: A randomized, open-label, single dose, 2-way crossover study was conducted in 50 healthy male subjects. Each sequence group consisted of 25 subjects, received a single oral 50 mg dose of Please Orally Soluble Film (test formulation) or VIAGRA(R) (reference formulation) by study period. Blood samples were obtained during a 24-hour period after dosing. Sildenafil and its metabolite concentrations were determined using validated LC-MS/MS. A non-compartmental pharmacokinetic analysis was performed. Safety was assessed through monitoring of adverse events, vital sign check-up, physical examination, laboratory tests and electrocardiography. RESULTS: All enrolled participants completed the study. The point estimates and 90% confidence intervals of log transformed C(max) and AUC(last) of the test formulation in comparison to those of reference formulation were 0.9294(0.8353 - 1.0341) and 0.9415 (0.8869 - 0.9994) respectively. The analysis of variance showed no significant influences of formulation, sequence and period on the pharmacokinetic parameters. The frequencies of adverse events were not statistically different between the formulations. No serious adverse event was observed or reported. CONCLUSION: Please Orally Soluble Film could be considered bioequivalent to VIAGRA(R) and had similar safety properties in healthy Korean male subjects.
Administration, Oral ; Citric Acid ; Cross-Over Studies ; Humans ; Male ; Physical Examination ; Piperazines ; Purines ; Sulfones ; Sildenafil Citratea ; Vital Signs

OBJECTIVESTo evaluate the outcome of treatment in patients with erectile dysfunction (ED) using sildenafil or intracavernosal injection of prostaglandin E1(PGE1).

METHODS54 patients with ED were randomly classified into two groups and received either oral sildenafil (group A) or intracavernosal injection of PGE1(group B) for 4-9 months with an average of 6 months.

RESULTSThe percentages of efficacy in the two groups were 80.0% and 83.3%, respectively. There was no statistical difference between group A and B (P > 0.05). Two of six patients who did not respond to sildenafal in group A achieved erections sufficient for sexual intercourse when the six patients received intracavernous injection of PGE1. None of the four patients who did not respond to intracavernous injection of PEG1 in group B achieved erection sufficient for sexual intercourse when they received oral sildenafil.

CONCLUSIONSBoth oral sildenafil and intracavernous injection of PGE1 are effective for patients with ED of various etiologies. The patients who do not respond to sildenafil can receive intracavernous injection therapy. The satisfactory results can probably achieved.

Administration, Oral ; Adult ; Aged ; Alprostadil ; therapeutic use ; Drug Administration Routes ; Erectile Dysfunction ; drug therapy ; Humans ; Male ; Middle Aged ; Piperazines ; therapeutic use ; Purines ; Sildenafil Citrate ; Sulfones ; Treatment Outcome

Administration, Inhalation ; Drug Therapy, Combination ; Female ; Hernias, Diaphragmatic, Congenital ; drug therapy ; Humans ; Infant, Newborn ; Male ; Nitric Oxide ; administration & dosage ; Piperazines ; administration & dosage ; Purines ; administration & dosage ; Sildenafil Citrate ; Sulfones ; administration & dosage

OBJECTIVETo evaluate the analgesic efficacy and systemic anti-inflammation of preoperative cyclooxygenase-2 nonsteroidal antiinflammatory drug, rofecoxib, after total knee replacement (TKR).

METHODSThirty patients underwent elective knee replacement were randomly given oral rofecoxib 25 mg (group RE, n = 15) or placebo (group E, n = 15) 1 hour prior to surgery. All patients received epidural combined isoflurane anesthesia during surgery and patient-controlled epidural analgesia after surgery for 72 hrs (0.1 mg/ml morphine + 1.2 mg/ml bupivacaine + 0.02 mg/ml droperidol). Modified verbal rate scale was used to evaluate postoperative pain intensity. The outcomes included pain scores during rest and movement of knee joints and analgesia satisfaction. Daily morphine consumption was recorded. Circulation leucocyte and serum cytokine concentrations (including interleukin 6, interleukin 8, interleukin 10, Tumor necrosis factor-alpha) were determined before surgery, at the end of surgery, 2 h, 6 h, 12 h, 24 h and 48 h after surgery in two groups using RIA. The amount of intraoperative blood loss and postoperative drainage from the knees were measured.

RESULTSThe pain scores were significantly less in the group RE than in group E during rest and knee joints movement on the first and second postoperative day, with an improvement in total analgesia satisfaction (P < 0.05). The mean dose of morphine for first 24 h was (8.1 +/- 1.5) mg in the E group and (6.8 +/- 0.7) mg in the RE group (t = -2.71, P < 0.01). Leucocyte and neutrophil counts were much higher in group E than in group RE at 12 h, 24 h post-operatively (P < 0.05). Serum TNF-alpha concentration was significantly lower in group RE than group E at the end of surgery, 6 h, 12 h postoperatively, as well as IL6 at 48 h, IL8 at 24h after surgery (P < 0.05). There were no significant differences in respect to the amount of intraoperative and postoperative blood loss between two groups (P > 0.05).

CONCLUSIONPreoperative cyclooxygenase-2-specific nonsteroidal anti-inflammatory drug rofecoxib increases analgesia satisfaction, reduces opioid requirement and demonstrates a systemic anti-inflammatory effect after TKR.

Administration, Oral ; Aged ; Analgesia, Epidural ; Anti-Inflammatory Agents ; Arthroplasty, Replacement, Knee ; Cyclooxygenase 2 Inhibitors ; administration & dosage ; Drug Therapy, Combination ; Female ; Humans ; Lactones ; administration & dosage ; Male ; Middle Aged ; Morphine ; administration & dosage ; Pain, Postoperative ; drug therapy ; prevention & control ; Premedication ; Sulfones ; administration & dosage

The possible characteristics of spinal interaction between sildenafil (phosphodiesterase 5 inhibitor) and morphine on formalin-induced nociception in rats was examined. Then the role of the opioid receptor in the effect of sildenafil was further investigated. Catheters were inserted into the intrathecal space of male Sprague-Dawley rats. For induction of pain, 50 microliter of 5% formalin solution was applied to the hindpaw. Isobolographic analysis was used for the evaluation of drug interaction between sildenafil and morphine. Furthermore, naloxone was intrathecally given to verify the involvement of the opioid receptor in the antinociception of sildenafil. Both sildenafil and morphine produced an antinociceptive effect during phase 1 and phase 2 in the formalin test. The isobolographic analysis revealed an additive interaction after intrathecal delivery of the sildenafil-morphine mixture in both phases. Intrathecal naloxone reversed the antinociception of sildenafil in both phases. These results suggest that sildenafil, morphine, and the mixture of the two drugs are effective against acute pain and facilitated pain state at the spinal level. Thus, the spinal combination of sildenafil with morphine may be useful in the management of the same state. Furthermore, the opioid receptor is contributable to the antinocieptive mechanism of sildenafil at the spinal level.
Analgesics/*administration & dosage ; Analgesics, Opioid/*administration & dosage ; Animals ; Behavior, Animal/drug effects ; Dose-Response Relationship, Drug ; Drug Synergism ; Formaldehyde/toxicity ; Injections, Spinal ; Male ; Morphine/*administration & dosage ; Naloxone/administration & dosage ; Narcotic Antagonists/administration & dosage ; Pain/chemically induced/therapy ; Pain Measurement/drug effects ; Phosphodiesterase Inhibitors/*administration & dosage ; Piperazines/*administration & dosage ; Purines/administration & dosage ; Rats ; Rats, Sprague-Dawley ; Sulfones/*administration & dosage ; Time Factors

OBJECTIVETo sum up the experience in administering oral tadalafil on alternate days for the treatment of erectile dysfunction (ED) that fails to respond to on-demand medication.

METHODSWe retrospectively analyzed the clinical data of 15 cases of ED treated with oral tadalafil on alternate days from September 2010 to March 2012. All the patients had failed to respond to on-demand medication of sildenafil previously.

RESULTSAfter 4 weeks of tadalafil treatment, 11 (73.3%) of the cases were remarkably improved, with significant difference in IIEF-5 scores before and after treatment (P < 0.05). Transient adverse reactions were observed in the other 4 cases, including mild headache in 2, slight backache in 1, and facial flush in 1.

CONCLUSIONOral tadalafil on alternate days is safe and effective in the treatment of ED that fails to respond to on-demand medication of sildenafil.

Administration, Oral ; Adult ; Carbolines ; administration & dosage ; therapeutic use ; Erectile Dysfunction ; drug therapy ; Humans ; Male ; Phosphodiesterase Inhibitors ; administration & dosage ; therapeutic use ; Piperazines ; therapeutic use ; Purines ; therapeutic use ; Retrospective Studies ; Sildenafil Citrate ; Sulfones ; therapeutic use ; Tadalafil ; Treatment Failure ; Treatment Outcome