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Randomized Controlled Trial
. 2019 Jul 24:13:2483-2490.
doi: 10.2147/DDDT.S209238. eCollection 2019.

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

Dongseong Shin  1   2   3 , Sang-In Park  4   5 , Hong-Sub Lee  6 , Kyung-Mi An  6 , Juyoung Jung  6 , MyongJae Lee  6 , Kyung-Sang Yu  3
Affiliations
Randomized Controlled Trial

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

Dongseong Shin et al. Drug Des Devel Ther. .

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 (AUC0-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 (Cmax) were decreased by 36.2%; however, AUC0-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: antibiotics; pharmacokinetics; phase I; peptide deformylase inhibitor.

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Conflict of interest statement

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.

Figures

Figure 1
Figure 1
Mean plasma concentration–time profiles of IDP-73152 after a single oral dose of 40, 80, 160, 320, 640, or 1280 mg of IDP-73152 mesylate. Bars represent standard deviations. (A) Plotted on a linear scale. (B) Plotted on a log scale.
Figure 2
Figure 2
Food effect on plasma IDP-73152 concentration after single oral administrations of 640 mg IDP-73152 mesylate. Bars represent standard deviations.
Figure 3
Figure 3
Linear regressions of IDP-73152 pharmacokinetic parameters after a single oral administration. (A) Relationship between individual Cmax and single oral dose of IDP-73152 mesylate. (B) Relationship between individual AUC0-t and single oral dose of IDP-73152 mesylate.
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