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Pharmacokinetic and Pharmacodynamic Properties of a New Long-Acting Granulocyte Colony-Stimulating Factor (HM10460A) in Healthy Volunteers

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Abstract

Background

HM10460A is a newly developed recombinant human granulocyte colony-stimulating factor with long-lasting characteristics. This factor is expected to be used for chemotherapy-related neutropenic conditions.

Objective

The aim of the present study was to evaluate the pharmacokinetics and pharmacodynamics of HM10460A following subcutaneous administration to healthy Korean subjects.

Methods

A randomized, double-blind, placebo-controlled, escalating single-dose study was conducted in 40 healthy Korean subjects. The subjects were allocated to single-dose groups of 5, 15, 45, 135 or 350 μg/kg, or placebo. Serial blood samples for pharmacokinetic/pharmacodynamic analyses were collected up to 22 days, and urine samples for pharmacokinetic analysis were collected up to 3 days after subcutaneous administration of HM10460A. The serum and urine concentrations were analyzed by enzyme-linked immunosorbent assay.

Results

Most of the serum concentrations in the 5 and 15 μg/kg dosing groups were below the lower limit of quantification (LLOQ). The median times to the peak concentration (Tmax) of HM10460A in the 45, 135, and 350 μg/kg dosing groups were 8.0, 14.0, and 24.0 h, respectively. The mean ± standard deviation values of the dose-normalized maximum concentration (Cmax) and dose-normalized area under the concentration-time curve (AUClast) for the 45, 135, and 350 μg/kg dosing groups were 14.13 ± 6.37, 66.19 ± 38.71, and 34.65 ± 19.69 μg/L/mg, respectively, and 265.0 ± 124.1, 2144 ± 1232, and 1386 ± 701.2 μg h/L/mg, respectively. The concentrations of HM10460A in the urine were below the LLOQ in all of the subjects. In all of the dosing groups, the area under the effect-time curve (AUEClast) of both the absolute neutrophil count (ANC) and the CD34+ cell count increased as the dose increased.

Conclusion

HM10460A showed dose-dependent pharmacokinetic characteristics, and the systemic exposure of HM10460A was positively correlated with the ANC and CD34+ cell counts.

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Author contributions:

Kwang-Hee Shin participated in the study design, conduct of the study, data analysis and interpretation of the data. Drs Kyung-Sang Yu, Sang-Goo Shin, and In-Jin Jang participated in the study design, data analysis and review of the manuscript. Drs Tae-Eun Kim and Kyoung Soo Lim contributed to the data interpretation and review of the manuscript. Drs Seo-Hyun Yoon and Joo Youn Cho contributed to the review of the bio-analysis data and manuscript. Drs Sei-Eun Kim and Kyung-Mi Park participated in the study design.

Disclosures:

This study was sponsored by Hanmi Pharmaceutical Co., Ltd., Seoul, Korea. Drs. Sei-Eun Kim, and Kyung-Mi Park are employers of Hanmi Pharmaceutical Co., Ltd. Other authors have no conflicts of interest to disclose.

Investigational site:

Clinical Trials Center, Seoul National University Hospital.

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Authors and Affiliations

  1. Department of Clinical Pharmacology and Therapeutics, Seoul National University College of Medicine and Hospital, 101 Daehak-ro, Jongno-gu, Seoul, 110-744, Korea

    Kwang-Hee Shin, Tae-Eun Kim, Kyoung Soo Lim, Seo-Hyun Yoon, Joo-Youn Cho, Sang-Goo Shin, In-Jin Jang & Kyung-Sang Yu

  2. Hanmi Pharmaceutical Co., Ltd., Seoul, Korea

    Sei-Eun Kim & Kyung-Mi Park

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  1. Kwang-Hee Shin
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Correspondence to Kyung-Sang Yu.

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Shin, KH., Kim, TE., Lim, K.S. et al. Pharmacokinetic and Pharmacodynamic Properties of a New Long-Acting Granulocyte Colony-Stimulating Factor (HM10460A) in Healthy Volunteers. BioDrugs 27, 149–158 (2013). https://doi.org/10.1007/s40259-013-0010-0

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