Effect of escalating doses of recombinant human granulocyte colony—stimulating factor (filgrastim) on circulating neutrophils in healthy subjects

Borleffs, Jan C. C.; Bosschaert, Mike A.R.; Vrehen, H. M.; Schneider, Margriet M E; Strijp, Jos van; Small, Maria; Borkett, Keith M.

doi:10.1016/s0149-2918(98)80135-5

Cited by 43 publications

(57 citation statements)

References 21 publications

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“…29,46,47 The G-CSF clearance has been shown to increase with the total mass of available receptors, which mainly depends on the number of mature neutrophils bearing these receptors. The assumption of such a specific elimination process in the model leads to G-CSF serum level dynamics that are in close agreement to pharmacokinetic measurements of Borleffs et al obtained in healthy subjects 48 (results not shown). Recently, a new polyethylene glycol conjugated filgrastim derivative (pegfilgrastim) has been developed with a markedly sustained duration of activity as compared with normal rhG-CSF.…”

Section: Discussionsupporting

confidence: 86%

A computational model of human granulopoiesis to simulate the hematotoxic effects of multicycle polychemotherapy

Engel¹,

Scholz²,

Loeffler³

2004

Blood

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Moderate intensification of conventional multicycle chemotherapy has recently been shown to improve treatment results in malignant lymphomas and might prove to be beneficial also in other malignancies. However, the feasibility of such regimens is mainly limited by their granulopoietic toxicity. To identify and quantify the basic cell kinetic mechanisms of damage and stimulation caused by cytotoxic drugs and recombinant human granulocyte colony-stimulating factor (rhG-CSF), respectively, we developed a mathematical model of human granulopoiesis that allows simulation of leukocyte concentration profiles under 10 different multicycle polychemotherapy regimens with varying drug composition, dosage, and scheduling, including rhG-CSF assistance. Clinical data on leukocyte profiles were obtained from large numbers of patients treated within several multicenter trials. Simulation studies show that the leukocyte profiles of all regimens can be appropriately fitted using one single set of assumptions and parameters for the cell kinetic effects of cytotoxic drugs and rhG-CSF. Furthermore, the model can be used to explain the interindividual heterogeneity of hematotoxicity by a differential chemosensitivity, which might be useful in drug scheduling for specific risk groups. It is demonstrated that the model can be used to design and to select new drug schedules for subsequent clinical trial testing.

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Section: Discussionsupporting

confidence: 86%

A computational model of human granulopoiesis to simulate the hematotoxic effects of multicycle polychemotherapy

Engel¹,

Scholz²,

Loeffler³

2004

Blood

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“…The effect of multiple dosing on the PK of filgrastim also was investigated [41]. Serum concentrations of filgrastim on day 1 were found to be substantially higher than on day 10, as shown by the higher peak concentrations (C max ) and AUC values ( Table 1).…”

Section: Pharmacokinetics Of Filgrastim In Healthy Volunteersmentioning

confidence: 99%

The Clinical Pharmacology of Filgrastim and Pegfilgrastim

Roskos¹

2011

Twenty Years of G-CSF

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“…The pharmacodynamics of Filgrastim were studied in normal volunteers at doses of 75, 150, 300, and 600 m g/day (approximately 1, 2, 4, and 8 m g/kg/day, respectively) for 10 days (36). A dose-related increase in peripheral neutrophil count above baseline was seen within 90 min of Filgrastim administration, reaching a peak approxim ately 12 h after administration.…”

Section: Clinical Pharmacokinetics and Pharmacodynamics Of Filgrastimmentioning

confidence: 99%

Biopharmaceutical Drug Development: Filgrastim (r-metHuG-CSF) Use in Patients with HIV Infection

Foote

Welch²

1999

Journal of Hematotherapy & Stem Cell Research

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Hematopoietic growth factors are well known to increase neutrophil counts and support the administration of myelotoxic and myelosuppressive therapies, especially chemotherapies. Filgrastim (r-metHuG-CSF) has been used in the setting of HIV disease to treat neutropenia and HIV-associated neutrophil defects. This article reviews the biology, product characteristics, and preclinical and clinical development of Filgrastim. Emphasis is given on the use of Filgrastim in the setting of HIV infection and AIDS.

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Effect of escalating doses of recombinant human granulocyte colony—stimulating factor (filgrastim) on circulating neutrophils in healthy subjects

Cited by 43 publications

References 21 publications

A computational model of human granulopoiesis to simulate the hematotoxic effects of multicycle polychemotherapy

A computational model of human granulopoiesis to simulate the hematotoxic effects of multicycle polychemotherapy

The Clinical Pharmacology of Filgrastim and Pegfilgrastim

Biopharmaceutical Drug Development: Filgrastim (r-metHuG-CSF) Use in Patients with HIV Infection

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