Selectivity of Avanafil, a PDE5 Inhibitor for the Treatment of Erectile Dysfunction: Implications for Clinical Safety and Improved Tolerability

Wang, Run; Burnett, Arthur L.; Heller, Warren; Omori, Kenji; Kotera, Jun; Kikkawa, Kohei; Yee, Shiyin; Day, Wesley W.; DiDonato, Karen; Peterson, Craig A.

doi:10.1111/j.1743-6109.2012.02822.x

Cited by 68 publications

(59 citation statements)

References 26 publications

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“…[13][14][15] Figure 4 summarizes the concentration-inhibition curves for tadalafil obtained from 3 in vitro studies, [13][14][15] in which the molar concentration of the drug was converted to mass concentration. When referring to the concentration-inhibition curves in Figure 4, the unbound postdose concentrations of tadalafil observed in our children (gray shaded region, corresponding to 5.9-146 nmol/L) were greater than the reported IC 50 values and seem to be clinically acceptable.…”

Section: Discussionmentioning

confidence: 99%

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Plasma Concentrations of Tadalafil in Children With Pulmonary Arterial Hypertension

Kohno¹,

Ichida²,

Hirono³

et al. 2014

Therapeutic Drug Monitoring

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We demonstrated variability in the total and unbound plasma concentrations of tadalafil in children. However, all children received the empirical doses of the drug; a mean dose of 0.97 mg·kg-1·d-1 showed sufficient unbound concentrations needed for half-maximal inhibition of human phosphodiesterase-5 in vitro. These observations may provide information for the proper use of tadalafil to treat children with PAH.

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Section: Discussionmentioning

confidence: 99%

“…The unbound concentrations found in routinely treated children with PAH were compared with the concentration-inhibition curves and/or IC 50 value for tadalafil against PDE5, which were obtained from 3 recent in vitro studies. [13][14][15] …”

Section: Introductionmentioning

confidence: 98%

Plasma Concentrations of Tadalafil in Children With Pulmonary Arterial Hypertension

Kohno¹,

Ichida²,

Hirono³

et al. 2014

Therapeutic Drug Monitoring

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“…9 Selectivity is expressed in terms of potency (IC 50 ) to inhibit PDE5 as opposed to inhibiting other isoenzymes of the PDE superfamily and is presented as a fold difference (Table 4). 33 A higher selectivity for PDE5 compared with other isozymes could translate into fewer adverse effects in clinical practice. PDEs are comprised of at least 11 families of enzymes that have been implicated in a broad range of cellular functions.…”

Section: Pharmacodynamicsmentioning

confidence: 99%

Pharmacotherapy for Erectile Dysfunction: Recommendations From the Fourth International Consultation for Sexual Medicine (ICSM 2015)

Hatzimouratidis

Salonia

Adaikan

et al. 2016

The Journal of Sexual Medicine

184

199

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Introduction Treatment of erectile dysfunction is based on pharmacotherapy for most patients. Aim To review the current data on pharmacotherapy for erectile dysfunction based on efficacy, psychosocial outcomes, and safety outcomes. Methods A review of the literature was undertaken by the committee members. All related articles were critically analyzed and discussed. Main Outcome Measures Levels of evidence (LEs) and grades of recommendations (GRs) are provided based on a thorough analysis of the literature and committee consensus. Results Ten recommendations are provided. (i) Phosphodiesterase type 5 (PDE5) inhibitors are effective, safe, and well-tolerated therapies for the treatment of men with erectile dysfunction (LE = 1, GR = A). (ii) There are no significant differences in efficacy, safety, and tolerability among PDE5 inhibitors (LE = 1, GR = A). (iii) PDE5 inhibitors are first-line therapy for most men with erectile dysfunction who do not have a specific contraindication to their use (LE = 3, GR = C). (iv) Intracavernosal injection therapy with alprostadil is an effective and well-tolerated treatment for men with erectile dysfunction (LE = 1, GR = A). (v) Intracavernosal injection therapy with alprostadil should be offered to patients as second-line therapy for erectile dysfunction (LE = 3, GR = C). (vi) Intraurethral and topical alprostadil are effective and well-tolerated treatments for men with erectile dysfunction (LE = 1, GR = A). (vii) Intraurethral and topical alprostadil should be considered second-line therapy for erectile dysfunction if available (LE = 3, GR = C). (viii) Dose titration of PDE5 inhibitors to the maximum tolerated dose is strongly recommended because it increases efficacy and satisfaction from treatment (LE = 2, GR = A). (ix) Treatment selection and follow-up should address the psychosocial profile and the needs and expectations of a patient for his sexual life. Shared decision making with the patient (and his partner) is strongly recommended (LE = 2, GR = A). (x) Counterfeit medicines are potentially dangerous. It is strongly recommended that physicians educate their patients to avoid taking any medication from unauthorized sources (LE = 2, GR = A). The first seven recommendations are the same as those from the Third International Consultation for Sexual Medicine and the last three are new recommendations. Conclusion PDE5 inhibitors remain a first-line treatment option because of their excellent efficacy and safety profile. This class of drugs is continually developed with new molecules and new formulations. Intracavernosal injections continue to be an established treatment modality, and intraurethral and topical alprostadil provide an alternative, less invasive treatment option.

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“…Tadalafil is a selective PDE5 inhibitor with a half-life of 17.5 h, which is longer than other available PDE5 inhibitors [16,17] . This property of tadalafil provides a wide window in which to engage in sexual intercourse.…”

Section: Discussionmentioning

confidence: 99%

Efficacy and Safety of Tadalafil Once-a-Day versus Tadalafil On-Demand in Patients with Erectile Dysfunction: A Systematic Review and Meta-Analyses

et al. 2017

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Introduction: To compare the efficacy and safety between tadalafil once-a-day and tadalafil on-demand dosing regimen in patients with ED. Materials and Methods: A systematic search of Medline, Embase, and Cochrane Library was performed to identify all randomized controlled trials (RCTs) that compared tadalafil used a once-a-day with an on-demand dosing regimen for erectile dysfunction. A secondary hand-search was performed in relevant journals, references, and the grey literature. Meta-analyses were performed using Review Manager version 5.3.0. Results: Six RCTs involving a total of 1,534 patients were included in this review. All studies reported the International Index of Erectile Function-Erectile Function domain score and the results of the meta-analysis showed no difference between the groups. The overall pooled estimated weighted mean differences (WMD) was 0.97 (95% CI -0.37 to 2.32; p = 0.16). Meta-analyses of Sexual Encounter Profile questions 2 and 3 (SEP-2 and SEP-3) showed that the once-a-day dosing regimen was superior to the on-demand regimen with statistical significance. The WMD of SEP-2 and SEP-3 were 10.32 (95% CI 3.16-17.48; p = 0.005) and 11.07 (95% CI 2.57-19.56; p = 0.01), respectively. Both dosing regimens of tadalafil showed similar complication rates. The meta-analyses of adverse events showed no significant differences. Conclusions: The efficacy rates of tadalafil once-a-day and on-demand were similar. No significant difference in safety was found between the 2 dose regimens of tadalafil.

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Selectivity of Avanafil, a PDE5 Inhibitor for the Treatment of Erectile Dysfunction: Implications for Clinical Safety and Improved Tolerability

Cited by 68 publications

References 26 publications

Plasma Concentrations of Tadalafil in Children With Pulmonary Arterial Hypertension

Plasma Concentrations of Tadalafil in Children With Pulmonary Arterial Hypertension

Pharmacotherapy for Erectile Dysfunction: Recommendations From the Fourth International Consultation for Sexual Medicine (ICSM 2015)

Efficacy and Safety of Tadalafil Once-a-Day versus Tadalafil On-Demand in Patients with Erectile Dysfunction: A Systematic Review and Meta-Analyses

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