Skip to main content
Key Specialties
Cardiology Diabetology Endocrinology Gastroenterology Geriatrics and Gerontology Gynecology and Obstetrics Hematology Infectious Disease Internal Medicine Nephrology Neurology Oncology Pediatrics Respiratory Medicine Rheumatology Surgery
Congress Coverage
2024 ACC Congress 2023 ESMO Congress 2023 EASD Congress 2023 ERS Congress 2023 ESC Congress
Clinical Collections
Advances in Alzheimer’s

Keynote webinar | Spotlight on medication adherence

LIVE: Thursday 27th June 2024, 18:00-19:30 (CEST)
Join our expert panel to discover why you need to understand the drivers of non-adherence in your patients, and how you can optimize medication adherence in your clinics to drastically improve patient outcomes.
ADVANCED SEARCH
Log in
Top
Clinical Drug Investigation
Published in: Clinical Drug Investigation 1/2014

01-01-2014 | Original Research Article

Pharmacokinetics, Safety and Tolerability of DA-6034, an Anti-Inflammatory Agent, After Single and Multiple Oral Administrations in Healthy Volunteers

Authors: Jieon Lee, Kwang-Hee Shin, Jung-Ryul Kim, Kyoung Soo Lim, In-Jin Jang, Jae-Yong Chung

Published in: Clinical Drug Investigation | Issue 1/2014

Login to get access

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.
Literature
1.
Mowat C, Cole A, Windsor A, et al. Guidelines for the management of inflammatory bowel disease in adults. Gut. 2011;60(5):571–607.PubMedCrossRef
2.
Hawthorne AB, Hawkey CJ. Immunosuppressive drugs in inflammatory bowel disease: a review of their mechanisms of efficacy and place in therapy. Drugs. 1989;38(2):267–88.PubMedCrossRef
3.
Rosenberg LN, Peppercorn MA. Efficacy and safety of drugs for ulcerative colitis. Expert Opin Drug Saf. 2010;9(4):573–92.PubMedCrossRef
4.
Wu CM. The chemical constituents of Artemisia species (III): isolation and identification of the lipophilic constituents from Artemisia argyi. Zhong Yao Tong Bao. 1985;10(1):31–2.PubMed
5.
Mota KS, Dias GE, Pinto ME, et al. Flavonoids with gastroprotective activity. Molecules. 2009;14(3):979–1012.PubMedCrossRef
6.
Kim YS, Son M, Ko JI, et al. Effect of DA-6034, a derivative of flavonoid, on experimental animal models of inflammatory bowel disease. Arch Pharm Res. 1999;22(4):354–60.PubMedCrossRef
7.
Nam SY, Kim JS, Kim JM, et al. DA-6034, a derivative of flavonoid, prevents and ameliorates dextran sulfate sodium-induced colitis and inhibits colon carcinogenesis. Exp Biol Med. 2008;233(2):180–91.CrossRef
8.
Ko SH, Yoo DY, Kim YJ, et al. A mechanism for the action of the compound DA-6034 on NF-kappaB pathway activation in Helicobacter pylori-infected gastric epithelial cells. Scand J Immunol. 2011;74(3):253–63.PubMedCrossRef
9.
Chung HJ, Choi YH, Choi HD, et al. Pharmacokinetics of DA-6034, an agent for inflammatory bowel disease, in rats and dogs: contribution of intestinal first-pass effect to low bioavailability in rats. Eur J Pharm Sci. 2006;27(4):363–74.PubMedCrossRef
10.
Yang SH, Bae SK, Kwon JW, Yoo M, Lee MG. Gender differences in the pharmacokinetics of DA-6034, a derivative of flavonoids, in rats. Biopharm Drug Dispos. 2006;27(1):47–51.PubMedCrossRef
11.
Nielsen OH, Verspaget HW, Elmgreen J. Inhibition of intestinal macrophage chemotaxis to leukotriene B4 by sulphasalazine, olsalazine, and 5-aminosalicylic acid. Aliment Pharmacol Ther. 1988;2(3):203–11.PubMedCrossRef
12.
Habal FM, Greenberg GR. Treatment of ulcerative colitis with oral 5-aminosalicylic acid including patients with adverse reactions to sulfasalazine. Am J Gastroenterol. 1988;83(1):15–9.PubMed
13.
Fasci Spurio F, Aratari A, Margagnoni G, Clemente V, Moretti A, Papi C. Low bioavailability and traditional systemic steroids in IBD: can the former take over the latter? J Gastrointestin Liver Dis. 2013;22(1):65–71.
14.
Ho GT, Chiam P, Drummond H, Loane J, Arnott ID, Satsangi J. The efficacy of corticosteroid therapy in inflammatory bowel disease: analysis of a 5-year UK inception cohort. Aliment Pharmacol Ther. 2006;24(2):319–30.PubMedCrossRef
Metadata
Title
Pharmacokinetics, Safety and Tolerability of DA-6034, an Anti-Inflammatory Agent, After Single and Multiple Oral Administrations in Healthy Volunteers
Authors
Jieon Lee
Kwang-Hee Shin
Jung-Ryul Kim
Kyoung Soo Lim
In-Jin Jang
Jae-Yong Chung
Publication date
01-01-2014
Publisher
Springer International Publishing
Published in
Clinical Drug Investigation / Issue 1/2014
Print ISSN: 1173-2563
Electronic ISSN: 1179-1918
DOI
https://doi.org/10.1007/s40261-013-0147-0

Other articles of this Issue 1/2014

Clinical Drug Investigation 1/2014 Go to the issue

Original Research Article

A Randomized, Double-Blind, Placebo-Controlled, Phase III Study of the Short-Acting β1-Adrenergic Receptor Blocker Landiolol Hydrochloride for Coronary Computed Tomography Angiography in Japanese Patients with Suspected Ischemic Cardiac Disease

Original Research Article

Apixaban, Dabigatran, and Rivaroxaban Versus Warfarin for Stroke Prevention in Non-Valvular Atrial Fibrillation: A Cost-Effectiveness Analysis

Original Research Article

Pharmacokinetics of Mirabegron, a β3-Adrenoceptor Agonist for Treatment of Overactive Bladder, in Healthy Japanese Male Subjects: Results from Single- and Multiple-Dose Studies

Original Research Article

RETRACTED ARTICLE: Interaction Study Between Finasteride and Tamsulosin in Healthy Young Male Subjects

Original Research Article

Pharmacodynamics and Pharmacokinetics of a Novel, Low-Dose, Soft-Gel Capsule of Acetylsalicylic Acid in Comparison with an Oral Solution After Single-Dose Administration to Healthy Volunteers: A Phase I, Two-Way Crossover Study

Original Research Article

Comparison of Algorithms for Oral Busulphan Area Under the Concentration–Time Curve Limited Sampling Estimate