Pharmacokinetic and pharmacodynamic analysis of subcutaneous recombinant human granulocyte colony stimulating factor (lenograstim) administration.
A total of 72 adult healthy volunteers were administered 1 microgram/kg of rhG-CSF. There was no correlation between Cmax 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.
Hayashi
N
N
Clinical Pharmacology Section, Chugai Pharmaceutical Co., Ltd., Tokyo, Japan.
Kinoshita
H
H
Yukawa
E
E
Higuchi
S
S
D000276:Adjuvants, Immunologic / Q000493:pharmacokinetics*; D000328:Adult; D000704:Analysis of Variance; D019540:Area Under Curve; D018592:Cross-Over Studies; D016179:Granulocyte Colony-Stimulating Factor / Q000493:pharmacokinetics*; D006801:Humans; D007279:Injections, Subcutaneous; D000078224:Lenograstim; D007958:Leukocyte Count / Q000187:drug effects; D008297:Male; D008657:Metabolic Clearance Rate; D009504:Neutrophils / Q000166:cytology / Q000187:drug effects; D011994:Recombinant Proteins / Q000493:pharmacokinetics
D000276:Adjuvants, Immunologic; D011994:Recombinant Proteins; D016179:Granulocyte Colony-Stimulating Factor; D000078224:Lenograstim