Pharmacokinetics and tolerability of IDP-73152 mesylate after a single oral administration under fasted and fed conditions in healthy volunteers

Abstract

Background and objective

IDP-73152 mesylate is a peptide deformylase inhibitor under investigation for the treatment of complicated skin and respiratory tract infections. The objective of this study was to investigate the pharmacokinetic (PK) profile and tolerability of IDP-73152 and the effect of food after a single oral administration.

Methods

A dose block-randomized, double-blind, placebo-controlled, dose-escalation study was conducted. A total of 56 healthy volunteers received IDP-73152 mesylate in a single oral dose of 40, 80, 160, 320, 640, or 1280 mg in the fasted and fed (640 mg only) states. Blood and urine samples for PK analysis were collected up to 48 h post dose.

Results

The area under the plasma concentration-time curve (AUC_0-t) of IDP-73152 increased in a dose-proportional manner in the range of 40–320 mg. The mean terminal half-life decreased from 10.7 to 6.2 hrs as the dose increased. The fraction excreted unchanged in the urine ranged from 0.05 to 0.12. In the 640-mg dose group, food delayed the median time to peak concentration (t_max) from 0.9 to 3.5 hrs. Furthermore, the maximum plasma concentration (C_max) were decreased by 36.2%; however, AUC_0-t was not generally affected. No serious adverse event or clinically significant findings were observed.

Conclusions

The systemic exposure of IDP-73152 proportionally increased as the dose increased up to 320 mg. The rate of absorption and extent of exposure were reduced by food intake. IDP-73152 was well tolerated without clinically significant adverse effects after a single oral administration.

Keywords:

• phase I
• pharmacokinetics
• antibiotics
• peptide deformylase inhibitor

Acknowledgments

This study was sponsored by Research Laboratories ILDONG Pharmaceutical Co., Ltd, Korea. This study was supported by a grant from the Korea Health Technology R&D Project through the Korea Health Industry Development Institute (KHIDI) and funded by the Ministry of Health & Welfare, Republic of Korea (grant number: HI14C2750).

Data availability

The datasets generated during the current study are available from the corresponding author on reasonable request.

Disclosure

MyongJae Lee reports personal fees from Research Laboratories ILDONG Pharmaceutical Co., Ltd., during the conduct of the study and personal fees from Research Laboratories ILDONG Pharmaceutical Co., Ltd., outside the submitted work. Hong-Sub Lee, Kyung-Mi An, Juyoung Jung and MyongJae Lee are employees of Research Laboratories ILDONG Pharmaceutical Co., Ltd. The authors report no other conflicts of interest in this work.