A Dose Block-randomized, Doubled, Placebo-controlled, Single Dose, Dose-escalation Clinical Phase I Study to Evaluate the Safety, Pharmacokinetics and Food

A dose block-randomized, double-blinded, placebo-controlled, single dose, dose-escalation clinical phase I study to evaluate the safety, pharmacokinetics and food effect of IDP-73152 mesylate after oral administration in healthy male volunteer

开始日期2013-07-01

申办/合作机构

Ildong Pharmaceutical Co., Ltd.

100 项与 IDP-73152 Mesylate 相关的临床结果

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100 项与 IDP-73152 Mesylate 相关的转化医学

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100 项与 IDP-73152 Mesylate 相关的专利（医药）

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项与 IDP-73152 Mesylate 相关的文献（医药）

2017-10-01·Journal of Pharmaceutical and Biomedical Analysis3区 · 医学

Quantification of IDP-73152, a novel antibiotic, in plasma from mice, rats and humans using an ultra-high performance liquid chromatography/tandem mass spectrometry method for use in pharmacokinetic studies

3区 · 医学

Article

作者: Lee, Hong-Sub ; Shin, Jeongcheol ; Lee, Myongjae ; Chung, Suk-Jae ; Kim, Dohee ; Park, Soobong ; Kang, Jae-Hoon ; Lee, Hee-Yeol

IDP-73152, a novel inhibitor of a bacterial peptide deformylase, was recently approved as a new, investigational drug in Korea for the clinical management of infections caused by Gram positive bacteria. The objective of this study was to develop/validate a simple and robust analytical method for the determination of IDP-73152 in plasma samples from rodents and humans, and to assess the feasibility of the assay for use in pharmacokinetic studies using animal models. Plasma samples were processed using a standard method for protein precipitation and an aliquot of the extract then injected onto an UHPLC-MS/MS system. The drug and IDP-117293, an internal standard, were analyzed in the positive ion-mode by electrospray ionization and quantified by monitoring the transition at m/z 555.2→245.2 for IDP-73152 and 563.3→253.1 for the internal standard, respectively. The lower and upper limit of the assay was determined to be 5 and 10000ng/ml, respectively, with an acceptable linearity (R>0.999) in the response-concentration relationship. Validation parameters, including accuracy, precision, dilution, recovery, matrix effect and stability were found to be within the acceptable ranges recommended by the assay validation guidelines of the United States FDA. The method was successfully applied to the quantification of IDP-73152 in plasma from mice/rats that had received a single oral administration of 80mg/kg IDP-73152, in the form of the mesylate salt. These findings suggest that the validated assay can be used in preclinical and clinical pharmacokinetic studies of IDP-73152.

Drug Design, Development and Therapy3区 · 医学

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

3区 · 医学

ArticleOA

作者: Yu, Kyung-Sang ; Jung, Juyoung ; Lee, MyongJae ; Lee, Hong-Sub ; Shin, Dongseong ; Park, Sang-In ; An, Kyung-Mi

BACKGROUND AND OBJECTIVEIDP-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.METHODSA 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.RESULTSThe 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.CONCLUSIONSThe 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.

Pharmaceutics

Prediction of Pharmacokinetics of IDP-73152 in Humans Using Physiologically-Based Pharmacokinetics

Article

作者: Lee, Myongjae ; Jeong, Yoo-Seong ; Chung, Suk-Jae ; An, Kyung-Mi ; Kim, Min-Soo

IDP-73152, a novel peptide deformylase inhibitor with an antibacterial effect against Gram-positive bacteria, is in phase I development. The objective of this study was to develop a physiologically-based pharmacokinetic model (PBPK) for IDP-73152 in animals, and to extend the model to humans. Biopharmaceutical properties of IDP-73152 are determined using in vitro/in vivo experimentations for the PBPK model. A transit model consisting of gastrointestinal segments is applied for an estimation of the intestinal absorption kinetics. The PBPK model of IDP-73152 in rats is able to appropriately predict the plasma concentration–time profiles after the administration of IDP-73152 at different doses and by different routes (combined absolute average fold error (cAAFE), 1.77). The model is also found to be adequate in predicting the plasma concentration–time profiles of IDP-73152 in mice (cAAFE 1.59) and dogs (cAAFE 1.42). Assuming the oral administration of IDP-73152 to humans at doses of 640 and 1280 mg, the model is able to reproduce the concentration–time profiles obtained in humans (cAAFE 1.38); therefore, these observations indicate that the PBPK model used for IDP-73152 is applicable to animal species and humans. This model may be useful in predicting efficacious doses of IDP-73152 for the management of infectious disease in humans.

100 项与 IDP-73152 Mesylate 相关的药物交易

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