madman
Super Moderator
ABSTRACT
Background: Erectile dysfunction (ED) is a relatively frequent disease that negatively impacts the overall quality of life, well-being, and relationships. Although the use of phosphodiesterase 5 inhibitors (PDE5is) has revolutionized the treatment of ED, a high percentage of ED patients discontinue PDE5i treatment.
Objectives: (i) To analyze the reasons for patient dissatisfaction leading to PDE5i discontinuation; (ii) analyze the pharmacokinetics of new formulations focusing on the time needed to reach an effective plasma concentration of PDE5is (T onset) following drug intake; and (iii) summarize the physicochemical properties of sildenafil to understand which excipients may increase the absorption rate.
Material and methods: An online PubMed literature search was conducted to identify English language publications from inception to January 2019.
Results: The main reasons for patient dissatisfaction when using PDE5is on demand are the relatively long Tonset after taking vardenafil and sildenafil, including formulations such as film-coated tablets, fine granules, orally disintegrating tablets (ODTs), and oral thin films (ODFs). The relatively long T onset, further worsened when accompanied by eating, highlights the following: (i) the need for planning intercourse, determining partner-related issues; (ii) issues when having sex before the maximum effect of the drug; and (iii) lower drug-related placebo effects. Some data suggest that sildenafil is a ‘difficult’ molecule, but T onset can be improved following absorption by buccal mucosa using appropriate excipients.
Conclusions: We conclude that several ODT and ODF formulations can improve the ‘discretion’ issue because they are taken without water, but they have similar pharmacokinetics to corresponding film-coated tablet formulations. One ODF formulation of sildenafil was characterized by a shorter T onset and could potentially increase patient satisfaction following treatment. However, more clinical studies are needed to confirm the findings. Surfactants and ascorbic acid appear to be crucial excipients for achieving a high absorption rate, but more studies are needed.
CONCLUSIONS
Rapid onset of the effects of PDE5is is a requirement when PDE5is are taken on demand. Most of the sildenafil formulations show too long T onset in fasting patients. In real life, patients tend to engage in sexual activity after an evening meal, which further slows the onset of the effects. Rapid onset of the effects of PDE5is can eliminate the need for planning intercourse, thereby increasing the spontaneity of sex and assisting the desire of both partners, and can increase the likelihood of a completely hard and fully rigid erection, resulting in increased sexual satisfaction. This could also improve the placebo effect connected with drug intake. To confirm that the rapid onset of the PDE5i effect plays a role in increasing patient satisfaction and decreasing treatment dropouts, head-to-head studies with blinded drug administration need to be performed.
It is likely that oral transmucosal drug delivery achieves a rapid onset of PDE5i effects, regardless of empty stomach. Moreover, this form allows greater discretion, as it does not require the intake of water. However, several ODT and ODF formulations of sildenafil exhibit pharmacokinetics that are very similar to those of film-coated tablets, probably because of the use of inappropriate excipients required by the peculiar physiochemical properties of sildenafil. Some evidence suggests that these formulations are mainly absorbed by the gastrointestinal route.
The pharmacokinetic profile of a more recent ODF formulation indicates rapid absorption via the oral mucosa, which likely achieves a more rapid onset of the sildenafil effects. However, head-to-head studies with blinded drug administration in patients before and after regular meals are needed.
Background: Erectile dysfunction (ED) is a relatively frequent disease that negatively impacts the overall quality of life, well-being, and relationships. Although the use of phosphodiesterase 5 inhibitors (PDE5is) has revolutionized the treatment of ED, a high percentage of ED patients discontinue PDE5i treatment.
Objectives: (i) To analyze the reasons for patient dissatisfaction leading to PDE5i discontinuation; (ii) analyze the pharmacokinetics of new formulations focusing on the time needed to reach an effective plasma concentration of PDE5is (T onset) following drug intake; and (iii) summarize the physicochemical properties of sildenafil to understand which excipients may increase the absorption rate.
Material and methods: An online PubMed literature search was conducted to identify English language publications from inception to January 2019.
Results: The main reasons for patient dissatisfaction when using PDE5is on demand are the relatively long Tonset after taking vardenafil and sildenafil, including formulations such as film-coated tablets, fine granules, orally disintegrating tablets (ODTs), and oral thin films (ODFs). The relatively long T onset, further worsened when accompanied by eating, highlights the following: (i) the need for planning intercourse, determining partner-related issues; (ii) issues when having sex before the maximum effect of the drug; and (iii) lower drug-related placebo effects. Some data suggest that sildenafil is a ‘difficult’ molecule, but T onset can be improved following absorption by buccal mucosa using appropriate excipients.
Conclusions: We conclude that several ODT and ODF formulations can improve the ‘discretion’ issue because they are taken without water, but they have similar pharmacokinetics to corresponding film-coated tablet formulations. One ODF formulation of sildenafil was characterized by a shorter T onset and could potentially increase patient satisfaction following treatment. However, more clinical studies are needed to confirm the findings. Surfactants and ascorbic acid appear to be crucial excipients for achieving a high absorption rate, but more studies are needed.
CONCLUSIONS
Rapid onset of the effects of PDE5is is a requirement when PDE5is are taken on demand. Most of the sildenafil formulations show too long T onset in fasting patients. In real life, patients tend to engage in sexual activity after an evening meal, which further slows the onset of the effects. Rapid onset of the effects of PDE5is can eliminate the need for planning intercourse, thereby increasing the spontaneity of sex and assisting the desire of both partners, and can increase the likelihood of a completely hard and fully rigid erection, resulting in increased sexual satisfaction. This could also improve the placebo effect connected with drug intake. To confirm that the rapid onset of the PDE5i effect plays a role in increasing patient satisfaction and decreasing treatment dropouts, head-to-head studies with blinded drug administration need to be performed.
It is likely that oral transmucosal drug delivery achieves a rapid onset of PDE5i effects, regardless of empty stomach. Moreover, this form allows greater discretion, as it does not require the intake of water. However, several ODT and ODF formulations of sildenafil exhibit pharmacokinetics that are very similar to those of film-coated tablets, probably because of the use of inappropriate excipients required by the peculiar physiochemical properties of sildenafil. Some evidence suggests that these formulations are mainly absorbed by the gastrointestinal route.
The pharmacokinetic profile of a more recent ODF formulation indicates rapid absorption via the oral mucosa, which likely achieves a more rapid onset of the sildenafil effects. However, head-to-head studies with blinded drug administration in patients before and after regular meals are needed.
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