Phase III Clinical Trial of KRN8601 (rhG-CSF) for Neutropenia in Patients with Human Immunodeficiency Virus Infection

Kimura, Satoshi; Shimada, Kaoru; Matsuda, Juzo; Gohchi, Kengo; Fukutake, K; Fukue, H; Okubo, Tomomi; Ishigatsubo, Yoshiaki; Yamada, Kouzou; Koitabashi, Yu

doi:10.11150/kansenshogakuzasshi1970.68.1093

Cited by 2 publications

(1 citation statement)

References 8 publications

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“…It has been suggested to become an efficacious drug for the treatment of malignant glioma [3][4][5], brain and lcptomeningeal tumours [6], breast cancer [7], malig nant lymphoma [8], neutropenia associated with HIV infection [9]. It has also been dem onstrated that urinary excretion of MX2 and its metabolites were extremely low [10], which may suggest a high retention rate of MX2 in vivo.…”

Section: Introductionmentioning

confidence: 99%

In vitro Binding of MX2 (KRN8602) and Epirubicin to Human Plasma Protein

Zhang

Cosolo²,

Zalcberg³

1997

Pharmacology

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This study compares the human plasma protein binding characteristics of MX2 and epirubicin. The binding characteristics were determined by equilibrium dialysis at various concentrations of the drugs. The binding dissociation constant (K_d),binding capacity (B_max) and partitioning constant (K_p) were obtained by Scatchard analysis of the free and bound drugs in the dialysis compartments. Our results have demonstrated that plasma protein binds epirubicin or MX2 in an unsatura-ble appearance over the concentration up to 150µmol/l. At the same concentrations, plasma protein binds more epirubicin than MX2. The nature of the interaction may consist of two classes of specific binding, and a partitioning. The binding dissociation constants were 18 and 17.5 µmol/l for the higher binding class (K_d1) and 315.8 and 316.9 µmol/l for the lower binding class (K_d2), respectively, for epirubicin and MX2. The respective maximum binding capacities (B_max) of plasma protein for epirubicin and MX2 were significantly different, 0.045 and 0.029 µmol/g protein for the higher binding class (Bmaxi), and 0.39 and 0.29 µmol/g protein for the lower binding class (B_max2). The partitioning constants (K_p) were 21.5 × 10^–5 and 20 × 10^–5 litres/g protein for epirubicin and MX2, respectively. The results suggest that plasma protein binds epirubicin or MX2 with a similar affinity, but has less binding sites for MX2. One contributing mechanism to the difference in activity noted between epirubicin and MX2 may be changes in free drug fractions.

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Section: Introductionmentioning

confidence: 99%

In vitro Binding of MX2 (KRN8602) and Epirubicin to Human Plasma Protein

Zhang

Cosolo²,

Zalcberg³

1997

Pharmacology

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Characterization of recombinant human granulocyte colony-stimulating factor expression by FT-IR spectroscopy: Studies on thermal induction and media formulation on the stability of the protein secondary structure

Vemula

Dedaniya

et al. 2016

Preparative Biochemistry & Biotechnology

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The Fourier-transform infrared (FT-IR) spectroscopic approach has been employed to understand the recombinant human G-CSF (rhG-CSF) protein accumulation, secondary structure, and thermal stability in Escherichia coli grown under a temperature shift strategy (37 and 28°C) in various media formulations. The choline + sodium pyruvate (37°C) and sodium pyruvate (28°C) formulations have shown the highest inclusion body (IB) accumulation of 0.41 and 0.46 mg/mL, respectively. Furthermore, insights on the structure of the rhG-CSF within IBs and intact cells have been investigated through secondary structure analysis. Thermal stability experiments were also carried out to explain the pattern of the second derivative structure of rhG-CSF. The studies showed that choline + sodium pyruvate formulation has preserved the protein secondary structure even at 82°C. Overall, the FT-IR spectroscopic technique can also be adopted to accelerate the characterization of other recombinant therapeutic proteins of E. coli origin.

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Phase III Clinical Trial of KRN8601 (rhG-CSF) for Neutropenia in Patients with Human Immunodeficiency Virus Infection

Cited by 2 publications

References 8 publications

In vitro Binding of MX2 (KRN8602) and Epirubicin to Human Plasma Protein

In vitro Binding of MX2 (KRN8602) and Epirubicin to Human Plasma Protein

Characterization of recombinant human granulocyte colony-stimulating factor expression by FT-IR spectroscopy: Studies on thermal induction and media formulation on the stability of the protein secondary structure

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