| Title |
Pharmacokinetics and tolerability of DA-8031, a novel selective serotonin reuptake inhibitor for premature ejaculation in healthy male subjects
|
|---|---|
| Published in |
Drug Design, Development and Therapy, March 2017
|
| DOI | 10.2147/dddt.s126861 |
| Pubmed ID | |
| Authors |
Dongseong Shin, SeungHwan Lee, Sojeong Yi, Seo Hyun Yoon, Joo-Youn Cho, Mi Young Bahng, In-Jin Jang, Kyung-Sang Yu |
| Abstract |
DA-8031 is a selective serotonin reuptake inhibitor under development for the treatment of premature ejaculation. This is the first-in-human study aimed at evaluating the pharmacokinetics and tolerability of DA-8031 and its metabolites (M1, M2, M4, and M5) in the plasma and urine after administration of a single oral dose in healthy male subjects. A dose block-randomized, double-blind, placebo-controlled, single ascending dose study was conducted. Subjects received either placebo or a single dose of DA-8031 at 5, 10, 20, 40, 60, 80, or 120 mg. DA-8031 and its four metabolites were analyzed in the plasma and urine for pharmacokinetic evaluation. The effect of genetic polymorphisms of cytochrome-P450 (CYP) enzymes on the pharmacokinetics of DA-8031 was evaluated. After a single dose, plasma DA-8031 reached the maximum concentration at a median of 2-3 h and was eliminated with terminal elimination half-life of 17.9-28.7 h. The mean renal clearance was 3.7-5.6 L/h. Dose-proportional pharmacokinetics was observed over the dose range of 20-80 mg. Among the metabolites, M4 had the greatest plasma concentration, followed by M5 and M1. Subjects with CYP2D6 intermediate metabolizer had significantly greater dose-normalized Cmax and AUC0-t of DA-8031 as well as smaller metabolic ratios than those subjects with CYP2D6 extensive metabolizer. The most common adverse events were nausea, dizziness, and headache, and no serious adverse events were reported. In conclusion, the systemic exposure of DA-8031 was increased proportionally to the dose within 20-80 mg. Genetic polymorphisms of CYP2D6 had an effect on the systemic exposure of DA-8031. DA-8031 was well tolerated after single doses of 80 mg or less. |
Mendeley readers
The data shown below were compiled from readership statistics for 20 Mendeley readers of this research output. Click here to see the associated Mendeley record.
Geographical breakdown
| Country | Count | As % |
|---|---|---|
| Unknown | 20 | 100% |
Demographic breakdown
| Readers by professional status | Count | As % |
|---|---|---|
| Researcher | 4 | 20% |
| Student > Bachelor | 2 | 10% |
| Student > Ph. D. Student | 2 | 10% |
| Unspecified | 1 | 5% |
| Student > Doctoral Student | 1 | 5% |
| Other | 2 | 10% |
| Unknown | 8 | 40% |
| Readers by discipline | Count | As % |
|---|---|---|
| Medicine and Dentistry | 7 | 35% |
| Biochemistry, Genetics and Molecular Biology | 2 | 10% |
| Pharmacology, Toxicology and Pharmaceutical Science | 1 | 5% |
| Agricultural and Biological Sciences | 1 | 5% |
| Unspecified | 1 | 5% |
| Other | 0 | 0% |
| Unknown | 8 | 40% |
Attention Score in Context
This research output has an Altmetric Attention Score of 1. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 27 November 2017.
All research outputs
#17,289,387
of 25,382,440 outputs
Outputs from Drug Design, Development and Therapy
#1,105
of 2,268 outputs
Outputs of similar age
#210,122
of 324,443 outputs
Outputs of similar age from Drug Design, Development and Therapy
#31
of 50 outputs
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