Do vardenafil and tadalafil have advantages over sildenafil in the treatment of erectile dysfunction?

Doggrell, Sheila A

doi:10.1038/sj.ijir.3901525

Cited by 35 publications

(22 citation statements)

References 154 publications

(212 reference statements)

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“…These inhibitors also have the same target and interact with many of the same residues at the active site of PDE5, as shown by the crystal structures of the isolated PDE5 catalytic domain in complex with silde-nafil and vardenafil (Sung et al, 2003;Card et al, 2004;Huai et al, 2004;Zhang et al, 2004;Wang et al, 2006). Although the head-to-head comparison is still lacking, the pharmacokinetic and pharmacodynamic analyses showed that these PDE5 inhibitors have similar efficacy and tolerance but exhibit some functional differences both in vitro and in vivo (Briganti et al, 2005;Shabsigh et al, 2006;Supuran et al, 2006;Wright, 2006;Doggrell, 2007;Mehrotra et al, 2007). For example, vardenafil shows 10-to 40-fold tighter binding with PDE5 than sildenafil and has an area under the curve of 74.5 g ⅐ h/liter at a 20-mg dosage compared with 1965 for sildenafil at a 100-mg dosage (Shabsigh et al, 2006;Mehrotra et al, 2007).…”

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confidence: 99%

Conformational Variations of Both Phosphodiesterase-5 and Inhibitors Provide the Structural Basis for the Physiological Effects of Vardenafil and Sildenafil

Wang¹,

Ye²,

Robinson³

et al. 2007

Mol Pharmacol

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Vardenafil has higher affinity to phosphodiesterase-5 (PDE5) than sildenafil and lower administered dosage for the treatment of erectile dysfunction. However, the molecular basis for these differences is puzzling because two drugs have similar chemical structures. Reported here is a crystal structure of the fully active and nonmutated PDE5A1 catalytic domain in complex with vardenafil. The structure shows that the conformation of the H-loop in the PDE5A1-vardenafil complex is different from those of any known structures of the unliganded PDE5 and its complexes with the inhibitors. In addition, the molecular configuration of vardenafil differs from that of sildenafil when bound to PDE5. It is noteworthy that the binding of vardenafil causes loss of the divalent metal ions that have been observed in all the previously published PDE structures. The conformational variation of both PDE5 and the inhibitors provides structural insight into the different potencies of the drugs.Cyclic nucleotide phosphodiesterases (PDEs) are key enzymes controlling cellular concentrations of the second messengers cAMP and cGMP (Mehats

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confidence: 99%

Conformational Variations of Both Phosphodiesterase-5 and Inhibitors Provide the Structural Basis for the Physiological Effects of Vardenafil and Sildenafil

Wang¹,

Ye²,

Robinson³

et al. 2007

Mol Pharmacol

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“…1). 1,2) cGMP level is important for the maintenance of erection because, together with nitric oxide (NO), it is involved in the relaxation of the smooth muscles of the corpus cavernosum. Udenafil (Zydena ® ), currently marketed in Korea, was developed by Dong-A Pharmaceutical Co. (Yongin, South Korea) for oral administration to male patients suffering from erectile dysfunction.…”

mentioning

confidence: 99%

Rapid and Sensitive Determination of Udenafil in Plasma by LC-MS/MS for Intranasal Pharmacokinetic Study in Rats

Cho

Yoon

et al. 2011

CHEMICAL & PHARMACEUTICAL BULLETIN

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A rapid and sensitive analytical method for udenafil in rat plasma was developed and validated using liquid chromatography-tandem mass spectrometry (LC-MS/MS). This chromatographic procedure was then applied to the in vivo pharmacokinetic studies in rats for determining the advantages of intranasal administration of the drug over oral administration. Using liquid-liquid extraction (LLE), udenafil and the internal standard (IS) sildenafil were extracted with dichloromethane from 100 m ml of plasma samples. Chromatographic separation was performed using Pursuit XRS C 18 column (50 mm؋2.1 mm, i.d., 3 m mm, Varian Inc., CA, U.S.A.) with an isocratic mobile phase consisting of acetonitrile and 10 mM ammonium acetate (90 : 10, v/v) at a flow rate of 0.2 ml/min over a total run time of 2.5 min. Detection and quantification was performed by mass spectrometry using the multiple reaction-monitoring mode at m/z 517.4→283.1 for udenafil and m/z 475.3→100.0 for IS. Results showed that the developed method was sensitive and specific for udenafil. Linearity was obtained in the range of 0.5-1000 ng/ml. The coefficient of variation of both intra-and inter-day validation were below 11.6% and the intraand inter-day accuracy ranged from 91.5 to 109.9%. Udenafil concentration was successfully measured from plasma after intranasal as well as after intravenous or oral administration at clinical dose (1.67 mg/kg) in rats. Moreover, the T max values obtained from pharmacokinetic studies suggested that administration of udenafil intranasally could be more effective than by the oral route.

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“…the three FDa-approved PDe5 inhibitors have been shown to be similarly effective in the treatment of eD. 77 there have been no trials comparing potential differences in treatment success after rP. reviews Sildenafil a few studies investigating the rehabilitative impact of sildenafil treatment after unilateral or bilateral nerve-sparing rP have been performed, and only one double-blind, randomized, placebo-controlled trial.…”

Section: Phosphodiesterase Type 5 Inhibitorsmentioning

confidence: 98%

Erectile dysfunction following prostatectomy: prevention and treatment

Magheli

Burnett²

2009

Nat Rev Urol

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Radical prostatectomy (RP) remains the standard treatment for men with clinically localized prostate cancer, despite the range of alternative treatment modalities. Even with significant advances in surgical technique and superb results for cancer control and preservation of urinary function, erectile dysfunction (ED) following RP is a common complication. This is mainly attributed to temporary cavernous nerve damage (neuropraxia) resulting in penile hypoxia, smooth muscle apoptosis, fibrosis and veno-occlusive dysfunction. One of the most promising new approaches is the concept of early penile rehabilitation, which is thought to prevent ED after RP by countering post-RP pathophysiological changes during the period of neural recovery. Various treatments, such as vacuum constriction devices, intraurethral and intracorporal alprostadil, and phosphodiesterase type 5 (PDE5) inhibitors, might serve to facilitate recovery of erectile function. PDE5 inhibitors are considered as the first-line treatment for early penile rehabilitation, with superior erectile function outcomes compared to placebo. Definitive conclusions regarding the success of penile rehabilitation cannot be drawn at this time because of differences in study design, data acquisition, and definitions of potency. Continued prospective, rigorous study is needed to develop and bring forward this important field and to establish the best evidence basis for counseling and treating patients suffering from ED after RP.

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Do vardenafil and tadalafil have advantages over sildenafil in the treatment of erectile dysfunction?

Cited by 35 publications

References 154 publications

Conformational Variations of Both Phosphodiesterase-5 and Inhibitors Provide the Structural Basis for the Physiological Effects of Vardenafil and Sildenafil

Conformational Variations of Both Phosphodiesterase-5 and Inhibitors Provide the Structural Basis for the Physiological Effects of Vardenafil and Sildenafil

Rapid and Sensitive Determination of Udenafil in Plasma by LC-MS/MS for Intranasal Pharmacokinetic Study in Rats

Erectile dysfunction following prostatectomy: prevention and treatment

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