Pharmacokinetics, Pharmacodynamics and Safety of JES9501 after Single and Multiple Oral Administration in Healthy Subjects.
10.12793/jkscpt.2013.21.2.141
- Author:
Anhye KIM
1
;
Bo Hyung KIM
;
Dongseong SHIN
;
Joo Youn CHO
;
Kyung Sang YU
;
In Jin JANG
;
Jae Yong CHUNG
Author Information
1. Department of Clinical Pharmacology and Therapeutics, Seoul National University College of Medicine and Hospital, Seoul, Korea.
- Publication Type:Randomized Controlled Trial ; Original Article
- Keywords:
Alzheimer disease;
Pharmacokinetics;
Pharmacodynamics;
Healthy volunteer
- MeSH:
Acetylcholinesterase;
Administration, Oral*;
Alzheimer Disease;
Area Under Curve;
Dosage Forms;
Evodia;
Humans;
Male;
Pharmacokinetics*;
Plasma
- From:Journal of Korean Society for Clinical Pharmacology and Therapeutics
2013;21(2):141-149
- CountryRepublic of Korea
- Language:Korean
-
Abstract:
BACKGROUND: JES9501 is dehydroevodiamine, the extract of Evodia rutaecarpa, expected to be a new therapeutic for Alzheimer disease. This study aims to investigate the pharmacokinetics (PK), pharmacodynamics (PD) and safety of JES9501 after single or multiple dosing. METHODS: A double-blind, randomized, placebo-controlled, dose ascending, parallel study was conducted in healthy subjects. A single dose of JES9501 50.100.200.400 or 800 mg and multiple doses of JES9501 100.200 or 400 mg once-daily for 7days was administered. Serial blood and urine samples for PK evaluation were collected. Acetylcholinesterase (AChE) activity was measured for PD evaluation in multiple dose group. RESULTS: In the single dose study, means of dose-normalized peak concentration (Cmax) of 100.200.400 and 800 mg dose group are comparable except 50 mg dose group. Means of dose-normalized area under the plasma concentration-time curve (AUC) from dosing to the last quantifiable concentration of corresponding dose group were similar. At steady state in the multiple dose study, means of dose-normalized Cmax and AUC for dosing interval of 100.200 and 400 mg dose group decreased as the dose increased, however those were not relevant. There was no significant difference of AChE activity between three dosage groups and placebo group. Adverse events related to study drug were all mild and there were no remarkable findings. CONCLUSION: JES9501 was safe and well-tolerated after single or multiple doses in healthy male subjects. Further studies are warranted to evaluate the PK of optimized dosage form and to prove the drug effect in clinical trials for Alzheimer disease patients.
