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Pharmacokinetic and Pharmacodynamic Analysis of Subcutaneous Recombinant Human Granulocyte Colony Stimulating Factor (Lenograstim) Administration
Author(s) -
Hayashi Naoto,
Kinoshita Haruki,
Yukawa Eiji,
Higuchi Shun
Publication year - 1999
Publication title -
the journal of clinical pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.92
H-Index - 116
eISSN - 1552-4604
pISSN - 0091-2700
DOI - 10.1177/00912709922008191
Subject(s) - pharmacokinetics , granulocyte colony stimulating factor , bioavailability , absolute neutrophil count , pharmacology , area under the curve , pharmacodynamics , granulocyte , elimination rate constant , absorption (acoustics) , medicine , toxicity , neutropenia , chemotherapy , volume of distribution , physics , acoustics
A total of 72 adult healthy volunteers were administered 1 μg/kg of rhG‐CSF. There was no correlation between C max and an increase in peripheral neutrophil count, and there was a negative correlation between AUC and this increase. The mechanism of this is probably based on the correlation between the elimination rate constant (ke) and neutrophil increase. The ke probably has a close relationship with uptake by neutrophil and its progenitor via the G‐CSF receptor. An individual with higher ke should therefore show a greater increase in neutrophil count. Therefore, AUC is proportional to the rhG‐CSF remainder, that is, the proportion that is not consumed in the course of increasing the neutrophil count. In such a situation, the bioavailability calculated from the AUC is unlikely to indicate the absorbed amount. The authors also analyzed the pharmacokinetics using a two‐compartment model with zero‐order absorption and first‐order elimination. This model was sufficient to obtain a good curve fit, and this demonstrates that the absorption process is not a first‐order but a zero‐order process. Therefore, there might be an upper limit to the rhG‐CSF transfer rate from subcutaneous tissue to blood.