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Pharmacokinetics, safety and tolerability of DA-6034, an anti-inflammatory agent, after single and multiple oral administrations in healthy volunteers.

Abstract：

BACKGROUND AND OBJECTIVES:Inflammatory bowel disease (IBD) is a chronic inflammatory disorder of the gastrointestinal tract. DA-6034 has been shown to be effective in an IBD model and has demonstrated a good toxicological profile in preclinical studies. This study evaluated the tolerability, safety and pharmacokinetics of DA-6034 in healthy volunteers. METHODS:A double-blind, randomized, placebo-controlled, ascending-dose study was conducted in 67 healthy volunteers. In the single-ascending-dose study, 10, 20, 50, 100 or 200 mg of DA-6034 was administered orally to 40 subjects; in the multiple-ascending-dose study, 40, 100 or 200 mg/day of DA-6034 was administered orally to 27 subjects for 7 days. Serial blood and urine samples were taken for pharmacokinetic analysis. Plasma drug concentrations were determined by high-performance liquid chromatography. Safety and tolerability were assessed throughout the study. RESULTS:DA-6034 had minimal absorption, and the pharmacokinetic parameters were highly variable among subjects. For both the single- and multiple-dose administrations, the coefficients of variation of the area under the plasma concentration-time curve to the last observation (AUClast) and the area under the plasma concentration-time curve over the dosing interval at steady state (AUCss,τ) ranged from 16.0 to 125.0 %. At doses of up to 200 mg of DA-6034, the mean maximum plasma concentration (C max) was <3 ng/mL, and the urine recovery ratio was 0.3 % of the dose, indicating a lack of absorption. Twenty-two mild adverse events were reported in 14 subjects. There were no serious adverse events and no significant changes in the safety assessment. CONCLUSION:DA-6034 was well tolerated and minimally absorbed in healthy volunteers. The non-systemic, local exposure of the gastrointestinal tract to DA-6034 may be advantageous for IBD treatment.

journal_name

Clin Drug Investig

journal_title

Clinical drug investigation

authors

Lee J,Shin KH,Kim JR,Lim KS,Jang IJ,Chung JY

doi

10.1007/s40261-013-0147-0

subject

Has Abstract

pub_date

2014-01-01 00:00:00

pages

37-42

issue

eissn

1173-2563

issn

1179-1918

journal_volume

pub_type

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Pharmacokinetics, safety and tolerability of DA-6034, an anti-inflammatory agent, after single and multiple oral administrations in healthy volunteers.