S. Park,1 D. Shin,2 Y. Choi,1 J. Kang,3 S. Park,3 J. Won,3 F. Jiang,1 H. Lee,1 I. Jiang,1 K. Yu1; 1Seoul National University College of Medicine and Hospital, Seoul, Korea, Republic of, 2Clinical Trials Center, Gachon University Gil Medical Center, Incheon, Korea, Republic of, 3Ildong Pharmaceutical Co., Ltd., Korea, Seoul, Korea, Republic of

BACKGROUND: IDP-73152 mesylate is a peptide deformylase inhibitor under clinical development for the treatment of complicated bacterial skin and respiratory tract infections. This study investigated the pharmacokinetic (PK) and tolerabililty profiles of IDP-73152 mesylate and the effect of food on them after a single oral administration.
METHODS: A dose block-randomized, double-blind, placebo-controlled, dose-escalation study was conducted in 56 healthy volunteers, who received a single oral dose of IDP-73152 mesylate at one of 40, 80, 160, 320, 640, and 1280 mg in the fasting and fed (640 mg only) states. Blood and urine samples for PK analysis were collected up to 48 hours post dose. Tolerability was assessed using adverse events (AEs), vital signs, electrocardiograms, and clinical laboratory tests.
RESULTS: The maximum plasma concentration (Cmax) and the area under the plasma concentration-time curve from 0 to 48 hours post dose (AUC0-48h) increased in a dose-proportional manner in the ranges of 40-640 mg and 40-320 mg, respectively. The mean terminal half-life decreased from 10.7 h to 6.2 h as the dose increased from 40 mg to 1280 mg. The fraction of IDP-73152 mesylate excreted unchanged in the urine ranged from 0.05-0.12. Food delayed the median time to peak concentration (Tmax) from 0.9 h to 3.5 h. Furthermore, food decreased Cmax and AUC0-48h by 36.2% and 13.8%, respectively. No serious AE or clinically significant change was noted.
CONCLUSION: The systemic exposure to IDP-73152 mesylate proportionally increased as the dose was increased up to 320 mg although it was decreased with food intake. IDP-73152 mesylate was well tolerated after a single oral administration.