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Randomized Controlled Trial
. 2017 Mar 10:11:713-723.
doi: 10.2147/DDDT.S126861. eCollection 2017.

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

Dongseong Shin  1 , SeungHwan Lee  2 , Sojeong Yi  2 , Seo Hyun Yoon  2 , Joo-Youn Cho  2 , Mi Young Bahng  3 , In-Jin Jang  2 , Kyung-Sang Yu  2
Affiliations
Randomized Controlled Trial

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

Dongseong Shin et al. Drug Des Devel Ther. .

Abstract

Objective: 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.

Methods: 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.

Results: 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.

Conclusion: 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.

Keywords: DA-8031; first-in-human; pharmacokinetics; premature ejaculation; selective serotonin reuptake inhibitor.

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Conflict of interest statement

Disclosure Mi Young Bahng is an employee of Dong-A ST. The other authors report no conflicts of interest in this work.

Figures

Figure 1
Figure 1
The chemical structures and the possible metabolic pathways of DA-8031 and its metabolites (M1, M2, M4, and M5) in human liver microsomes.
Figure 2
Figure 2
Mean plasma concentration–time profiles of DA-8031, following a single oral dose of 5, 10, 20, 40, 60, 80, or 120 mg. Note: Bars represent standard deviations.
Figure 3
Figure 3
Mean (A) QTcB and (B) QTcF interval-time profiles after a single oral administration or either placebo or DA-8031 at doses of 5, 10, 20, 40, 60, 80, or 120 mg. The relationship between either (C) QTcB or (D) QTcF and the time-matched plasma concentration of DA-8031. Note: Bars represent standard deviations.
See this image and copyright information in PMC

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