fortimicin-a-sulfate and nartograstim

KW-2228, a mutationally modified recombinant human granulocyte colony-stimulating factor (rhG-CSF), possesses some excellent properties such as high specific activity in stimulating granulocyte colony-formation in vitro, great biological stability in plasma, good pharmacokinetic profile and high potency in granulopoiesis in normal mice in vivo. Recently, the application of G-CSF against infectious diseases has been considered, and some animal experiments have been carried out to support such an application on human infectious diseases. In this paper, we examined combination effect of KW-2228 with various chemotherapeutic drugs in experimental infectious in mice. A combination effect of KW-2228 with ceftazidime (CAZ) was evaluated in a systemic infection with Pseudomonas aeruginosa in normal mice. Combination effects of KW-2228 with CAZ, astromicin and amphotericin B were also evaluated in experimental systemic infections caused by P. aeruginosa, Serratia marcescens and Candida albicans in immunosuppressed mice treated with cyclophosphamide. Synergistic effects were generally observed at KW-2228 doses from 1 to 5 micrograms per mouse with all combinations. We concluded that combination therapies of KW-2228 with various chemotherapeutic drugs in experimental infections in mice showed that it should be effective in normal and immunosuppressed host. These results of our laboratory studies suggest that KW-2228 in combination with antibiotics would be useful in the clinical treatment of microbial infections. Recently, clinical efficacy studies of KW-2228 have been initiated in Japan.

Topics: Aminoglycosides; Amphotericin B; Animals; Anti-Bacterial Agents; Candidiasis; Ceftazidime; Drug Therapy, Combination; Granulocyte Colony-Stimulating Factor; Male; Mice; Mice, Inbred Strains; Neutropenia; Pseudomonas Infections; Recombinant Proteins; Serratia Infections

A modified recombinant human granulocyte colony-stimulating factor (rhG-CSF), KW-2228, has some excellent properties such as high specific activity in stimulating granulocyte colony-formation in vitro, great biological stability in plasma, good pharmacokinetic profile and high potency in granulopoiesis in normal mice in vivo. Recently, the application of G-CSF against infectious diseases has been considered, and some animal experiments have been carried out to support its clinical applications. Patients with underlying diseases such as leukemia and cancer often have recurrent infections because of reduced numbers or functions of neutrophils, which mediate an early stage of host defense. In out present study, we established a new method to evaluate in vivo potency of G-CSF in colon 26 tumor-bearing mice. By using the method, we examined combination effects of KW-2228 with aminoglycoside antibiotics against a systemic infection caused by Pseudomonas aeruginosa. KW-2228 (1 microgram/mouse/day) was administered (s.c.) once a day for 4 days before the bacterial infection was introduced in colon 26 tumor-bearing mice receiving cyclophosphamide 3 days after the transplantation of tumor. Antibiotics were administered (s.c.) 2 hours after the introduction of the bacterial infection. ED50 of gentamicin (GM) alone and that of the combination with KW-2228 were 40.7 mg/kg and 3.6 mg/kg, respectively. ED50 of astromicin (ASTM) alone and that of the combination with KW-2228 were 386 mg/kg and 17.8 mg/kg, respectively. Thus the combination therapy of KW-2228 with GM or ASTM exhibited excellent protective effects in comparison to the treatment with antibiotic alone.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Aminoglycosides; Animals; Anti-Bacterial Agents; Cyclophosphamide; Drug Therapy, Combination; Gentamicins; Granulocyte Colony-Stimulating Factor; Male; Mice; Mice, Inbred BALB C; Neoplasm Transplantation; Neoplasms, Experimental; Neutropenia; Pseudomonas Infections; Recombinant Proteins