Vardenafil preclinical trial data: potency, pharmacodynamics, pharmacokinetics, and adverse events

Bischoff, Erwin

doi:10.1038/sj.ijir.3901213

Cited by 74 publications

(53 citation statements)

References 19 publications

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“…According to the toxicokinetic results, these differences may due to gender differences in drug metabolism. Other PDE5 inhibitors, such as sildenafil, vardenafil and avanafil, undergo hepatic metabolism via the CYP3A4 pathway, but no gender difference was reported [21][22][23]. Thus, further research is needed concerning the mechanism of action and metabolism of yonkenafil hydrochloride.…”

Section: Journal Of Biomedical Sciences Issn 2254-609xmentioning

confidence: 99%

A 90-day Repeat-Dose Oral Toxicity Study of Yonkenafil Hydrochloride in Beagle Dogs

Liu¹,

Jin²,

Yu³

et al. 2017

J Biomedical Sci

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Yonkenafil hydrochloride, a novel synthetic phosphodiesterase type 5 inhibitor, is a promising drug for the treatment of erectile dysfunction. The repeated-dose toxicity of yonkenafil hydrochloride was assessed in male and female beagle dogs. Twenty-four dogs were randomly allocated to four groups and administered yonkenafil hydrochloride orally at dosages of 0, 7, 30 or 120 mg/kg/day for 90 days followed by a 28-day recovery period. During the test period, clinical signs, mortality, body weight, food consumption, ophthalmoscopy, electrocardiography, hematology, serum biochemistry, urinalysis, organ weights, gross findings and histopathology were examined. There were no abnormal changes in the clinical observations except that gastrointestinal intolerance was observed in the 120 mg/kg/day group. The laboratory and histopathological examinations revealed yonkenafil hydrochloride toxicity to various organs, including the thyroid gland, liver, prostate, uterus and breast; at the end of the recovery period, this damage was resolved. The level of yonkenafil hydrochloride that resulted in no observable adverse effects in beagle dogs was 7 mg/kg/day.

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Section: Journal Of Biomedical Sciences Issn 2254-609xmentioning

confidence: 99%

A 90-day Repeat-Dose Oral Toxicity Study of Yonkenafil Hydrochloride in Beagle Dogs

Liu¹,

Jin²,

Yu³

et al. 2017

J Biomedical Sci

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“…The fraction, F 3-5 was obtained from the ethanolic extract of A. ulei root bark according to a previously described procedure. 22 1 H NMR analysis of this fraction (F [3][4][5] ) revealed the presence of three major indole-type alkaloids, which were identified as uleine, nor-uleine and tetrahydro-3,14,4,21-elipticin ( Figure 1) based on spectral details and in comparison with literature data. 24 …”

Section: Methodsmentioning

confidence: 99%

“…In separate experiments, when once a stable contraction to PHE (1 mM) was attained, F [3][4][5] (100 mg ml À1 ) was added to the organ bath in the presence of vehicle or one of the following pharmacological blockers: 10 mM atropine, 100 mM L-NAME, 100 mM ODQ, 100 mM glibenclamide, 1 mM TTX or 10 mM apamin plus 100 nM charibdotoxin. The cavernosal strips were preincubated with these pharmacological agents in the bath chamber for a 30 min period before the addition of F [3][4][5] .…”

Section: Chemicalsmentioning

confidence: 99%

“…The cavernosal strips were preincubated with these pharmacological agents in the bath chamber for a 30 min period before the addition of F [3][4][5] .…”

Section: Chemicalsmentioning

confidence: 99%

“…In recent years, the selective phosphodiesterase 5 (PDE 5 ) inhibitors, sildenafil, tadalafil and vardenafil have become the treatment option for ED but their uses have contraindications, such as with concomitant nitrate administration or a-adrenergic blockers. 4 Besides, there were reports of undesirable cardiovascular and visual disturbances 5,6 presumably due to differential expression of phosphodiesterase enzymes in various tissues and their selectivity. Therefore, alternative forms of medical treatment remain clinically interesting, including plant extracts, which many patients prefer as a treatment modality.…”

Section: Introductionmentioning

confidence: 99%

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Relaxant effects of an alkaloid-rich fraction from Aspidosperma ulei root bark on isolated rabbit corpus cavernosum

et al. 2007

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We described earlier that an alkaloid-rich fraction (F 3-5 ) from Aspidosperma ulei (Markgr) induces penile erection-like behavioral responses in mice. This study verified a possible relaxant effect of this fraction on isolated rabbit corpus cavernosum (RbCC) strips precontracted by phenylephrine (1 lM) or K þ 60 mM. F 3-5 (1-300 lg ml À1 ) relaxed the RbCC strips in a concentration-dependent and reversible manner. The relaxant effect of F 3-5 (100 lg ml À1 ) on phenylephrine contraction was unaffected in the presence of atropine, N-x-nitro-L-arginine methyl ester or 1H-[1,2,4]oxadiazole[4,3-a] quinoxalin-1-one and by preincubation with tetrodotoxin, glibenclamide, apamine and charybdotoxin suggesting that mechanisms other than cholinergic, nitrergic, sGC activation or potassium channel opening are probably involved. However, the phasic component of the contraction induced by K þ 60 mM as well as the maximal contraction elicited by increasing external Ca 2 þ concentrations in depolarized corpora cavernosa was inhibited by F 3-5 . We conclude that F 3-5 relaxes the RbCC smooth muscle, at least in part, through a blockade of calcium influx or its function.

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Phosphodiesterase inhibitors for erectile dysfunction in patients with diabetes mellitus

Vardi

Nini

2007

Cochrane Database of Systematic Reviews

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Background Erectile dysfunction is a common multi-factorial complication of diabetes mellitus. Numerous strategies have been tried to overcome this diabetic complication. In recent years, phosphodiesterase type 5 (PDE-5) inhibitors have been introduced in the management of erectile dysfunction. Objectives The objective of this review was to assess the effect of PDE-5 inhibitors on the management of erectile dysfunction in diabetic men. Search methods Studies were obtained from computerised searches of MEDLINE, EMBASE and The Cochrane Library. Selection criteria Randomised controlled trials, in which treatment with PDE-5 inhibitors was compared to control, in diabetic patients with erectile dysfunction. Data collection and analysis Two reviewers independently extracted data and assessed trial quality. Main results Eight randomised controlled trials were identified. A total 976 men were allocated to receive a PDE-5 inhibitor and 741 were randomised to the control groups. Overall, 80% of the participants suffered from type 2 diabetes mellitus. The weighted mean difference (WMD) for the International Index of Erectile Function (IIEF) questions 3 and 4 (frequency of penetration during and maintaining erection to completion of intercourse) was 0.9 (95% CI 0.8 to 1.1) and 1.1 (95% CI 1.0 to 1.2) at the end of the study period, in favour of the intervention group. The WMD for the IIEF erectile dysfunction domain at the end of the study period was 6.6 (95% CI 5.2 to 7.9) in favour of the PDE-5 inhibitors arm. The relative risk (RR) for answering "yes" to a global efficacy question ("did the treatment improve your erections?") was 3.8 (CI 95% 3.1 to 4.5) in the PDE-5 inhibitors compared with the control arm. The WMD between the percentage of successful attempts in the PDE-5 inhibitors and in the control arm was 26.7 (95% CI 23.1 to 30.3). Mortality was not reported in any of the included trials. Adverse cardiovascular effects were reported in one study. Headache was the most frequent adverse event reported, flushing was the second most common event, with upper respiratory tract complaints and flu like syndromes, dyspepsia, myalgia, abnormal vision and back pain also reported in a descending order of frequency. The overall risk ratio for developing any adverse reaction was 4.8 (CI 95% 3.74 to 6.16) in the PDE-5 inhibitors arm as compared to the control. Phosphodiesterase inhibitors for erectile dysfunction in patients with diabetes mellitus (Review)

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Vardenafil preclinical trial data: potency, pharmacodynamics, pharmacokinetics, and adverse events

Cited by 74 publications

References 19 publications

A 90-day Repeat-Dose Oral Toxicity Study of Yonkenafil Hydrochloride in Beagle Dogs

A 90-day Repeat-Dose Oral Toxicity Study of Yonkenafil Hydrochloride in Beagle Dogs

Relaxant effects of an alkaloid-rich fraction from Aspidosperma ulei root bark on isolated rabbit corpus cavernosum

Phosphodiesterase inhibitors for erectile dysfunction in patients with diabetes mellitus

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