Objective: To develope and validate a reliable and sensitive liquid chromatography-tandem mass spectrometry (LC-MS/MS) method for determination of vardenafil concentration in plasma of rat. Methods: Plasma samples of normal Sprague-Dawley rats were collected. A Phenomenex Synergi Polar-RP 80A column (2.0 mm×50 mm, 4 µm) was used. Column temperature was set at 30 ℃. Mobile phase A was 0.1% formic acid in water; mobile phase B was 0.1% formic acid in acetonitrile. The flow rate was 0.4 ml/minutes. Quantitative determination was performed by electrospray ionization, operating in positive ion multiple reaction monitoring (MRM) mode. Cisapride was used as the internal standard. The feasibility of the method was evaluated by examining its specificity, linearity and quantitative range, precision and accuracy, matrix effects, and stability. Results: Under the selected chromatographic and mass spectrometry conditions, the monitoring ions of vardenafil and internal standard were mass-to-charge ratio（m/z) 489.3/151.2 and 466.4/234.2, the retention times of vardenafil and internal standard were 2.62 and 2.80 minutes, respectively, and the peak shape was satisfactory. The method has good linearity in the concentration range of 0.2-200 ng/ml. The intra-batch precision (%CV) and accuracy (%DEV) of vardenafil were 1.5%-9.7% and -6.8%-6.6%, respectively. The inter-batch precision and accuracy of vardenafil were 3.1% -8.4% and -3.7%-4.6%, respectively. In this sample processing method, the extraction recovery rate of vardenafil was obtained at range of 88.2%-104.6%, which met the requirements for the investigation of extraction recovery rate. In this sample processing method, the normalized matrix factor of each quality control concentration of vardenafil was 1.04, 0.85, and 1.04, and the coefficient of variation (%CV) was in the range of 1.7%-10.7%, which met the requirements for the investigation of matrix effects. Variations of short-term stability, long-term stability, and stability of 4 freeze-thaw cycles of vardenafil was within ±15%, and the coefficient of variation were within 5%. Conclusion: The high performance liquid chromatography-tandem mass spectrometry method established in this study is feasible for the measurement of concentration of vardenafil in rat plasma and this method has good specificity and high accuracy, and can be used to detect the concentration of vardenafil in rat plasma.
Animals ; Chromatography, Liquid ; Feasibility Studies ; Rats ; Rats, Sprague-Dawley ; Reproducibility of Results ; Sensitivity and Specificity ; Tandem Mass Spectrometry ; Vardenafil Dihydrochloride

PURPOSE: To examine the association between phosphodiesterase type 5 (PDE5) inhibitor use and melanoma by 1) conducting a systematic review of observational studies; and 2) determining if low PDE5A gene expression in human melanoma correlated with decreased overall survival. MATERIALS AND METHODS: A systematic search of observational studies examining the association between PDE5 inhibitor use and melanoma was performed through ClinicalTrials.gov, the Cochrane Library, EMBASE, PubMed, and Web of Science databases, and seven eligible studies were identified. PDE5A gene expression was analyzed with RNA sequencing data from 471 human melanoma samples obtained from The Cancer Genome Atlas. RESULTS: Four studies reported a positive association between PDE5 inhibitor use and melanoma, and three studies found no correlation. RNA sequencing data analysis revealed that under-expression of the PDE5A gene did not impact clinical outcomes in melanoma. CONCLUSIONS: There is currently no evidence to suggest that PDE5 inhibition in patients causes increased risk for melanoma. The few observational studies that demonstrated a positive association between PDE5 inhibitor use and melanoma often failed to account for major confounders. Nonetheless, the substantial evidence implicating PDE5 inhibition in the cyclic guanosine monophosphate (cGMP)-mediated melanoma pathway warrants further investigation in the clinical setting.
Gene Expression ; Genome ; Guanosine Monophosphate ; Humans ; Melanoma ; Phosphodiesterase 5 Inhibitors ; Sequence Analysis, RNA ; Sildenafil Citrate ; Statistics as Topic ; Tadalafil ; Vardenafil Dihydrochloride

Phosphodiesterase type 5 (PDE5) inhibitors are the most commonly used treatment for erectile dysfunction (ED). Since the launch of sildenafil, several drugs-including mirodenafil, sildenafil citrate (sildenafil), tadalafil, vardenafil HCL (vardenafil), udenafil, and avanafil-have become available. Mirodenafil is a newly developed pyrrolopyrimidinone compound, which is a potent, reversible, and selective oral PDE5 inhibitor. Mirodenafil was launched in Korea in 2007, and an orally disintegrating film of mirodenafil was developed in 2011 for benefitting patients having difficulty in swallowing tablets. This study aimed to review the pharmacokinetic characteristic profile of mirodenafil and report evidence on its efficacy in the case of ED. In addition, we reviewed randomized controlled studies of mirodenafil's daily administration and efficacy for lower urinary tract symptoms.
Citric Acid ; Deglutition ; Erectile Dysfunction* ; Humans ; Korea ; Lower Urinary Tract Symptoms ; Male ; Phosphodiesterase 5 Inhibitors ; Tablets ; Treatment Outcome ; Sildenafil Citrate ; Tadalafil ; Vardenafil Dihydrochloride

ABCC10, also known as multidrug-resistant protein 7 (MRP7), is the tenth member of the C subfamily of the ATP-binding cassette (ABC) superfamily. ABCC10 mediates multidrug resistance (MDR) in cancer cells by preventing the intracellular accumulation of certain antitumor drugs. The ABCC10 transporter is a 171-kDa protein that is localized on the basolateral cell membrane. ABCC10 is a broad-specificity transporter of xenobiotics, including antitumor drugs, such as taxanes, epothilone B, vinca alkaloids, and cytarabine, as well as modulators of the estrogen pathway, such as tamoxifen. In recent years, ABCC10 inhibitors, including cepharanthine, lapatinib, erlotinib, nilotinib, imatinib, sildenafil, and vardenafil, have been reported to overcome ABCC10-mediated MDR. This review discusses some recent and clinically relevant aspects of the ABCC10 drug efflux transporter from the perspective of current chemotherapy, particularly its inhibition by tyrosine kinase inhibitors and phosphodiesterase type 5 inhibitors.
Antineoplastic Agents ; Benzamides ; Benzylisoquinolines ; Drug Resistance, Multiple ; Drug Resistance, Neoplasm ; Erlotinib Hydrochloride ; Humans ; Imatinib Mesylate ; Imidazoles ; Multidrug Resistance-Associated Proteins ; antagonists & inhibitors ; Piperazines ; Purines ; Pyrimidines ; Quinazolines ; Sildenafil Citrate ; Sulfonamides ; Sulfones ; Taxoids ; Triazines ; Vardenafil Dihydrochloride

OBJECTIVETo evaluate phosphodiesterase type 5 (PDE5) inhibitors in the management of temporary penile erectile dysfunction (ED) in patients undergoing assisted reproductive technology (ART).

METHODSThis study included 75 male patients that experienced ejaculation failure due to temporary ED during ART treatment. We treated the patients with PDE5 inhibitors sildenafil, tadanafil and vardenafil, and then evaluated the hardness of penile erection using Erection Hardness Score (EHS) and analyzed the end-point efficacy.

RESULTSSildenafil was administered to 28 of the patients, tadanafil to 25, and vardenafil to 22. Of the total number of patients, 61 (81.3%) achieved effective erection, but no significant differences were observed in the rate of effectiveness among the sildenafil (24 cases, 85.7%), tadanafil (20 cases, 80.0%) and vardenafil (17 cases, 77.3%) groups (P > 0.05). After medication, 53 (70.7%) of the patients successfully ejaculated, but there were no remarkable differences in the success rate among the sildenafil (21 cases, 75.0%), tadanafil (17 cases, 68.0%) and vardenafil (15 cases, 68.2%) groups (P > 0.05). Of the 75 patients, 37 received the recommended initial dose and 38 the maximum recommended dose of PDE5 inhibitors, but no significant differences were found in the rate of successful sperm retrieval between the former (28 cases, 75.7%) and the latter group (25 cases, 65.8%) (P > 0.05). Mild adverse events, including transient flush and dizziness, occurred in 5 cases (6.7%).

CONCLUSIONPDE5 inhibitors can help temporary ED patients to achieve penile erection and ejaculation during ART treatment.

Ejaculation ; Erectile Dysfunction ; drug therapy ; Humans ; Imidazoles ; therapeutic use ; Male ; Phosphodiesterase 5 Inhibitors ; therapeutic use ; Piperazines ; therapeutic use ; Purines ; therapeutic use ; Reproductive Techniques, Assisted ; Sildenafil Citrate ; Sulfonamides ; therapeutic use ; Sulfones ; therapeutic use ; Triazines ; therapeutic use ; Vardenafil Dihydrochloride

Currently, phosphodiesterase type 5 (PDE5) inhibitors are the initial treatment option for erectile dysfunction. The reported efficacy of PDE5 inhibitors is about 70%, although it is significantly lower in difficult-to-treat subpopulations. Treatment failures might be due to the severity of the underlying pathophysiology, improper use of medication, unrealistic patient expectations, difficult relationship dynamics, severe performance anxiety, and other psychological problems. Physicians must address these issues to identify true treatment failures attributable to the drugs. This article discusses factors that might affect the response to PDE5 inhibitors and develops a strategy to maximize the overall efficacy of PDE5 inhibitors in initial non-responders to PDE5 inhibitors.
Carbolines ; Erectile Dysfunction ; Humans ; Imidazoles ; Male ; Performance Anxiety ; Phosphodiesterase 5 Inhibitors ; Piperazines ; Purines ; Sulfones ; Treatment Failure ; Triazines ; Sildenafil Citrate ; Tadalafil ; Vardenafil Dihydrochloride

BACKGROUND/AIMS: To evaluate the effects of the phosphodiesterase type 5 (PDE5) inhibitor vardenafil on esophageal function, including bolus transit, using multichannel intraluminal impedance and esophageal manometry (MII-EM). METHODS: Sixteen healthy volunteers (15 men) underwent an MII-EM study including 10 liquid swallows and 10 viscous swallows in a seated position after fasting. Then, each subject was asked to ingest 50 mL distilled water or 10 mg vardenafil dissolved in 50 mL water, in a double-blind manner. After 25 minutes, the MII-EM study was repeated. RESULTS: Eight men received vardenafil and eight subjects received water. Resting and residual lower esophageal sphincter pressures differed significantly only in the vardenafil group (from 18 +/- 6.7 to 6.6 +/- 5.3 mmHg, P < 0.001 and from 4.9 +/- 2.6 to 2.1 +/- 3.6 mmHg, P = 0.006, respectively). Mean distal esophageal amplitude decreased significantly only in the vardenafil group (from 86.7 +/- 41.6 to 34.0 +/- 38.0 mmHg, P < 0.05). Complete bolus transits of liquid and viscous meals decreased significantly only after vardenafil ingestion (from 80.2% +/- 13.8% to 49.4% +/- 27.9%, P < 0.05 and from 72.8% +/- 33.6% to 21.5% +/- 29.0%, P = 0.01, respectively). CONCLUSIONS: Vardenafil decreased esophageal bolus transit in the seated position, despite decreased lower esophageal sphincter pressure.
Eating ; Electric Impedance ; Esophageal Sphincter, Lower ; Fasting ; Humans ; Imidazoles ; Male ; Manometry ; Meals ; Piperazines ; Sulfones ; Swallows ; Triazines ; Water ; Vardenafil Dihydrochloride

OBJECTIVETo evaluate the efficacy and safety of long-term on-demand use of vardenafil in the treatment of erectile dysfunction (ED).

METHODSWe conducted a questionnaire investigation among 891 ED patients treated by on-demand use of oral vardenafil at 20 mg every 3 days from March 2007 to January 2010, covering the general information of the patients, their need for and attitudes towards the treatment, clinical efficacy and adverse events of the drug, and satisfaction of the patients and their partners after 12 weeks of treatment.

RESULTSTreatment and follow-up were completed in 700 patients, of whom 504 (72%) achieved sufficient hardness and duration of penile erection and overall sexual satisfaction, 84 (12%) admitted to improvement of erectile hardness and duration but not adequate satisfaction, and the other 112 (16%) experienced no significant changes. Significant differences were found in IIEF-5 scores, Rigiscan test results and partners TSS scores before and after the treatment (P < 0.05). Most frequent adverse events included flushing (15%), dizziness and headache (10%), dyspepsia (3%), and nasal congestion (1%).

CONCLUSIONLong-term on-demand use of oral vardenafil, in addition to its safety and good tolerance, can effectively improve the erectile function of ED patients, their success rate of sexual intercourse, and overall quality of sexual life.

Adult ; Erectile Dysfunction ; drug therapy ; Follow-Up Studies ; Humans ; Imidazoles ; adverse effects ; therapeutic use ; Male ; Piperazines ; adverse effects ; therapeutic use ; Sulfones ; adverse effects ; therapeutic use ; Treatment Outcome ; Triazines ; adverse effects ; therapeutic use ; Vardenafil Dihydrochloride ; Vasodilator Agents ; adverse effects ; therapeutic use ; Young Adult

OBJECTIVETo investigate the impact of penile surgery on the erectile function of the patient and to evaluate the role of small-dose vardenafil in restoring the impaired penile erection.

METHODSSixty cases of penile cavernosum surgery were equally and randomly divided into a vardenafil and a control group, the former treated 5 - 7 days after surgery with 10 mg vardenafil every other day, while the latter given vitamin E at 100 mg once a day, both for 12 weeks. The penile erectile function of the patients was evaluated with the IIEF-5 questionnaire before surgery and at 3 and 6 months after vardenafil medication.

RESULTSThe mean IIEF-5 scores of the vardenafil group were 18.83 +/- 2.98 and 20.13 +/- 2.98 at 3 and 6 months after vardenafil medication, significantly higher than 14.21 +/- 3.62 before surgery (P > 0.05), while that of the control group was significantly decreased at 3 months as compared with the preoperative score (13.38 +/- 2.82 versus 15.80 +/- 3.02, P < 0.05). The vardenafil group showed the highest IIEF-5 score after surgery (P < 0.05).

CONCLUSIONLong-term administration of small-dose vardenafil after penile surgery helps to restore and maintain penile erectile function.

Adult ; Erectile Dysfunction ; drug therapy ; Humans ; Imidazoles ; administration & dosage ; therapeutic use ; Male ; Middle Aged ; Penile Erection ; Penis ; surgery ; Piperazines ; administration & dosage ; therapeutic use ; Postoperative Period ; Recovery of Function ; Sulfones ; administration & dosage ; therapeutic use ; Treatment Outcome ; Triazines ; administration & dosage ; therapeutic use ; Vardenafil Dihydrochloride ; Vasodilator Agents ; administration & dosage ; therapeutic use

PURPOSE: We analyzed the prescriptions of alpha-blockers and phosphodiesterase 5 inhibitors (PDE5Is) in the urology department as well as in other departments of the general hospital. METHODS: We investigated the frequency of prescription of alpha-blockers and PDE5Is from 3 general hospitals from January 1, 2007 to December 31, 2009. For alpha-blockers, data were collected from patients to whom alpha-blockers were prescribed from among patients recorded as having benign prostatic hyperplasia according to the 5th Korean Standard Classification of Diseases. For PDE5Is, data were collected from patients to whom PDE5Is were prescribed by the urology department and by other departments. Alpha-blockers were classified into tamsulosin, alfuzosin, doxazosin, and terazosin, whereas PDE5Is were classified into sildenafil, tadalafil, vardenafil, udenafil, and mirodenafil. RESULTS: Alpha-blockers were prescribed to 11,436 patients in total over 3 years, and the total frequency of prescriptions was 68,565. Among other departments, the nephrology department had the highest frequency of prescription of 3,225 (4.7%), followed by the cardiology (3,101, 4.5%), neurology (2,576, 3.8%), endocrinology (2,400, 3.5%), pulmonology (1,102, 1.6%), and family medicine (915, 1.3%) departments in order. PDE5Is were prescribed to 2,854 patients in total over 3 years, and the total frequency of prescriptions was 10,558. The prescription frequency from the urology department was 4,900 (46.4%). Among other departments, the endocrinology department showed the highest prescription frequency of 3,488 (33.0%), followed by the neurology (542, 5.1%), cardiology (467, 4.4%), and family medicine (407, 3.9%) departments in order. CONCLUSIONS: A high percentage of prescriptions of alpha-blockers and PDE5Is were from other departments. For more specialized medical care by urologists is required in the treatment of lower urinary tract symptoms and erectile dysfunction.
Adrenergic alpha-1 Receptor Antagonists ; Carbolines ; Cardiology ; Cyclic Nucleotide Phosphodiesterases, Type 5 ; Doxazosin ; Endocrinology ; Erectile Dysfunction ; Hospitals, General ; Humans ; Imidazoles ; Lower Urinary Tract Symptoms ; Male ; Nephrology ; Neurology ; Phosphodiesterase 5 Inhibitors ; Piperazines ; Prazosin ; Prescriptions ; Prostatic Hyperplasia ; Pulmonary Medicine ; Purines ; Pyrimidines ; Quinazolines ; Sildenafil Citrate ; Sulfonamides ; Sulfones ; Tadalafil ; Triazines ; Urology ; Vardenafil Dihydrochloride