world-biomarkers-pharma-biotech-2017-posters

11 / 61

Volume10, Issue 12 (Suppl) J Proteomics Bioinform, an open access journal
ISSN: 0974-276X
Page 67
conferenceseries.com
World Biomarkers & Pharma Biotech 2017
December 07-09, 2017
December 07-09, 2017 | Madrid, Spain
&
20th International Conference on
PHARMACEUTICAL BIOTECHNOLOGY
9th WORLD BIOMARKERS CONGRESS
JOINT EVENT ON
An accelerator mass spectrometry-enabled micro-tracer study to evaluate the human mass balance
of KD101, an anti-obesity drug under development
Howard Lee1, Jun Gi Hwang1, Anhye Kim2, and Stephen R Dueker 3
1Seoul National University College of Medicine and Hospital, Korea
2Ajou University Medical Center, Korea
3Biocore, Korea
In clinical drug development, it is important to understand the absorption, distribution, metabolism and excretion (ADME)
properties of a drug in humans. The micro-tracer study based on the accelerator mass spectrometry (AMS) is an ultrasensitive
technique to obtain human ADME profiles with a negligible radiation dose. KD101 is a novel compound under development
to treat obesity. The aim of this study was to investigate the absorption, metabolism and excretion properties of KD101 in obese
subjects. A randomized, open-label, single-dose, one-treatment, one-period, one-sequence study was conducted in six males
with a BMI ≥27, who received KD101 at 400 mg with 3.52 µg of [14C]-KD101 (180 nCi) in the fed state. Plasma, urine and
feces samples were collected up to 288 hours post-dose for mass balance and metabolite profiling. Plasma concentrations of
KD101 were determined using a validated GC method. Total radioactivity in the samples was determined using AMS. Safety
and tolerability was evaluated based on vital signs, adverse events, clinical laboratory tests, and electrocardiography. All of the
subjects completed the study with no clinically significant safety issue. Mean total recovery rate (range) was 85.21% (75.36-
99.01%), consisting of 77.96% (68.31-92.33 %) for urine and 7.26% (5.91-8.51%) for feces, which differed greatly from the pre-
clinical data. Oral absorption of [14C]-KD101 was rapid with the peak plasma concentration reaching at 5.83h post dose, which
was consistent with the previous report. In the urine radiochromatogram, five large peaks were identified including a peak
represented by the parent compound. KD101 is excreted predominantly through the urine in humans. Many of the excreted
materials in the urine were considered metabolites. This study demonstrated effectiveness of the micro-tracer study enabled by
AMS in humans to investigate the ADME property of KD101, which hugely differed from that seen in the preclinical animals.
Recent Publications:
1. Kim Y K, Kim A, Park S J, Lee H (2017) New tablet formulation of tacrolimus with smaller interindividual variability
may become a better treatment option than the conventional capsule formulation in organ transplant patients. Drug
Design Dev Ther. (11): 2861-2869.
2. Kim Y, Kim A, Lee S, Choi S H, Lee D Y, Song J S, Lee H, Jang I J, Yu K S (2017) Pharmacokinetics, Safety and
Tolerability of Tedizolid Phosphate After Single-Dose Administration in Healthy Korean Male Subjects. Clin Ther. 39
(9): 1849-1857.
3. Lee H, Chung H, Lee S, Lee H, Yang S M, Yoon S h, Cho J Y, Jang I J, Yu K S (2017) LBEC0101, A Proposed Etanercept
Biosimilar: Pharmacokinetics, Immunogenicity, and Tolerability Profiles Compared with a Reference Biologic Product
in Healthy Male Subjects. BioDrugs. DOI: 10.1007/s40259-017-0230-9.
4. Yi S, Lee H, Jang S B, Byun H M, Yoon S H, Cho J Y, Jang I J and Yu K S (2017) A novel K+ competitive acid blocker,
YH4808, sustains inhibition of gastric acid secretion with a faster onset than esomeprazole: randomized clinical study
in healthy volunteers. Aliment Pharmacol Ther. doi: 10.1111/apt.14148.
5. Oh J, Lee S, Lee H, Cho J Y and Yoon S H (2017) The novel carboxylesterase 1 variant c.662A>C may decrease the
bioactivation of oseltamivir n humans. PLoS on. 12 (4): 0176320.
Biography
Howard Lee is the Founder and Director of the Center for Convergence Approaches in Drug Development (CCADD). He serves as a Professor at the Department of
Transdisciplinary Studies, Graduate School of Convergence Science and Technology, Seoul National University. He is also appointed at Seoul National University
College of Medicine and Hospital, affiliated with the Department of Clinical Pharmacology and Therapeutics. He previously served as the Head of Global Strategy
and Planning, Clinical Trials Center, SNUH. As of August 2017, he was appointed as Chair of the Graduate Program in Clinical Pharmacology, Seoul National
University. He has spearhead the introduction of Accelerator Mass Spectrometry (AMS)-enabled exploratory early clinical drug development studies to the Korean
biopharmaceutical R&D sector, which has awarded him two government grants.
Howard Lee et al., J Proteomics Bioinform 2017, 10:12(Suppl)
DOI: 10.4172/0974-276X-C1-110