Pharmacokinetics and tolerability of DA-8031, a novel selective serotonin reuptake inhibitor for premature ejaculation in healthy male subjects

Shin, Dong Wan; Lee, Seung Hwan; Yi, Sangho; Yoon, Seo Hyun; Cho, Joo Youn; Bahng, Mi Young; Jang, In Jin; Yu, Kyung‐Sang

doi:10.2147/dddt.s126861

Cited by 7 publications

(15 citation statements)

References 27 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The commonest adverse events were nausea and hypotension. The authors found that a dose of 120 mg was associated with prolongation of the QT interval on electrocardiogram 88 . This is potentially a very exciting drug for the future, and further studies are awaited ( Table 5 ).…”

Section: Management Options: Novel Agentsmentioning

confidence: 99%

“…In addition, it is associated with reduced serotonin transporter occupancy, confirmed on positron emission tomography of the rat brain 87 . This was recently evaluated in the first human trial to assess safety and tolerability after a single dose in healthy men 88 . Men were randomly assigned to receive either the active drug or placebo.…”

Section: Management Options: Novel Agentsmentioning

confidence: 99%

See 1 more Smart Citation

Premature ejaculation: challenging new and the old concepts

et al. 2017

View full text Add to dashboard Cite

Premature ejaculation remains a difficult condition to manage for patients, their partners, and the clinician. Whilst prevalence rates are estimated to be 20–40%, determining a diagnosis of premature ejaculation is difficult, as the definition remains both subjective and ill-defined in the clinical context. As our understanding of the ejaculatory pathway has improved, new opportunities to treat the condition have evolved with mixed results. In this review, we explore some of these controversies surrounding the aetiology, diagnosis, and treatment of this condition and discuss potential novel therapeutic options.

show abstract

Section: Management Options: Novel Agentsmentioning

confidence: 99%

Section: Management Options: Novel Agentsmentioning

confidence: 99%

Premature ejaculation: challenging new and the old concepts

et al. 2017

View full text Add to dashboard Cite

show abstract

“…DA-8031 is a novel SSRI for the treatment of PE. 15 , 16 In a preclinical study in rats, DA-8031 delayed the latency to ejaculation. 15 In a first-in-human single ascending dose clinical study, DA-8031 was rapidly absorbed at a median time of 2–3 h and eliminated with a mean terminal t 1/2 of 17.9–28.7 h with a dose range of 5–120 mg.…”

Section: Introductionmentioning

confidence: 99%

“…Although QT prolongation was observed after a single dose of 120 mg, DA-8031 was well tolerated after single doses of 80 mg or less. 16 …”

Section: Introductionmentioning

confidence: 99%

Pharmacokinetics, Tolerability and Pharmacogenetics of DA-8031 After Multiple Ascending Doses in Healthy Male Subjects

Hwang

Lee²,

Cho³

et al. 2021

DDDT

Self Cite

View full text Add to dashboard Cite

Purpose DA-8031 is a novel selective serotonin reuptake inhibitor for the treatment of premature ejaculation. This study investigated the pharmacokinetics, safety and tolerability of multiple oral doses of DA-8031. In addition, a genetic analysis was explored to evaluate the effect of genetic polymorphisms on the pharmacokinetics of DA-8031. Subjects and Methods A dose block-randomized, double-blind, placebo-controlled study was conducted in 3 dose groups with 20, 30 and 40 mg of DA-8031. Healthy male subjects were randomized to DA-8031 or placebo at a 4:1 ratio in each dose group of 10 subjects by oral administration once daily for 7 consecutive days. Serial blood and urine samples were collected for the pharmacokinetic evaluation, and the pharmacokinetic-related genes were analyzed by DMET TM plus. A safety evaluation was conducted including adverse events (AEs) monitoring and 12-lead electrocardiogram (ECG). Results The plasma DA-8031 concentration reached the maximum concentration (C max ) in 2.2 to 3.0 h and was eliminated with a mean half-life of 25.5 to 26.7 h at steady state. The accumulation index of DA-8031 ranged 2.3 to 2.8. The systemic exposure of DA-8031 of the CYP2D6 intermediate metabolizer (IM) was significantly higher compared to the CYP2D6 poor metabolizer (PM). There were no clinically significant QTc interval changes, and all the adverse events were mild. Conclusion After multiple oral doses of DA-8031 20, 30, and 40 mg in this study, the systemic exposure of DA-8031 increased in a more than dose-proportional manner with the increasing doses, and DA-8031 was generally well tolerated. In addition, the genetic polymorphisms of CYP2D6 have an impact on the pharmacokinetics of DA-8031.

show abstract

“…Dapoxetine has some minor "on demand" efficacy but clearly is not a breakthrough medicine in the treatment of PE [11]. Another SSRI, with a comparable profile as dapoxetine, DA-8031 is in development for PE, but efficacy data have not yet been elucidated [12,13]. Several other approaches for treatment of PE are used or are in development, including local anesthetics (e.g., lidocaine) used as cream, gel, or spray, and are moderately effective in delaying ejaculation [10].…”

mentioning

confidence: 99%

Introductory Chapter: Sexual Dysfunction - Introduction and Perspective

Olivier¹

2017

Sexual Dysfunction

View full text Add to dashboard Cite

Psychiatric Association [1] gives the following classifications of sexual dysfunctions: delayed ejaculation, erectile disorder, female orgasmic disorder, female sexual interest/arousal disorder, genito-pelvic pain/penetration disorder, male hypoactive sexual desire disorder, premature (early) ejaculation, substance-/medication-induced sexual dysfunction, other specified sexual dysfunction, and unspecified sexual dysfunction. It is evident that sexual dysfunctions constitute a heterogeneous group of disorders. They are characterized by clinically significant disturbances to respond sexually or experience sexual pleasure. Determining the character of the sexual dysfunction is a complex issue, which needs extensive clinical and psychological/ psychiatric expertise in order to come to a correct clinical judgment and includes partner and relationship factors, individual vulnerability, psychiatric comorbidity, stressors, and cultural, religious, and medical factors.Sexual functioning involves a complex interaction of biological, sociocultural, and psychological factors, which makes a clear diagnosis sometimes rather difficult. In any case, problems should be ruled out that are caused by interfering factors, like drugs, medicines, a medical condition (e.g., pelvic nerve damage) or external factors like partner violence, or other severe stressors.

show abstract

Pharmacokinetics and tolerability of DA-8031, a novel selective serotonin reuptake inhibitor for premature ejaculation in healthy male subjects

Cited by 7 publications

References 27 publications

Premature ejaculation: challenging new and the old concepts

Premature ejaculation: challenging new and the old concepts

Pharmacokinetics, Tolerability and Pharmacogenetics of DA-8031 After Multiple Ascending Doses in Healthy Male Subjects

Introductory Chapter: Sexual Dysfunction - Introduction and Perspective

Contact Info

Product

Resources

About