TY - JOUR
T1 - Pharmacokinetics, safety and tolerability of DA-6034, an anti-inflammatory agent, after single and multiple oral administrations in healthy volunteers
AU - Lee, Jieon
AU - Shin, Kwang Hee
AU - Kim, Jung Ryul
AU - Lim, Kyoung Soo
AU - Jang, In Jin
AU - Chung, Jae Yong
PY - 2014/1
Y1 - 2014/1
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=84891840611&partnerID=8YFLogxK
U2 - 10.1007/s40261-013-0147-0
DO - 10.1007/s40261-013-0147-0
M3 - Article
C2 - 24158940
AN - SCOPUS:84891840611
SN - 1173-2563
VL - 34
SP - 37
EP - 42
JO - Clinical Drug Investigation
JF - Clinical Drug Investigation
IS - 1
ER -