The effects and pharmacokinetics of rhG-CSF in patients with chronic renal failure.
The pharmacokinetics and effects of recombinant human granulocyte colony-stimulating factor (rhG-CSF) on neutrophils and immunological function were studied in 10 patients with end-stage renal failure. A single dose and 2-week consecutive dosing of 50 micrograms/m2 of rhG-CSF were drip infused intravenously, and plasma rhG-CSF levels, peripheral blood cell counts, coagulation, and neutrophil and immunological functions were determined during treatment. The mean half-life of rhG-CSF in patients (2.47 +/- 0.64 h) was prolonged to about twice that of healthy subjects, and hemodialysis did not affect the pharmacokinetics. A marked increase in neutrophils and a slight increase in lymphocytes were observed with the single and consecutive administration of rhG-CSF, but no significant changes were noted in other leukocyte fractions and erythrocyte and platelet counts. The neutrophil alkaline phosphatase value increased significantly following rhG-CSF administration, and other neutrophil functions were also ameliorated in several patients with neutrophil dysfunction. In consecutive administration, however, mild bone pain and increased serum alkaline phosphatase were observed in about half the patients, but neither accumulation of rhG-CSF nor antibody production was detected. From these results, it is concluded that rhG-CSF is safe and effective for the treatment of neutropenia and neutrophil dysfunction in patients with renal failure.
Akizawa
T
T
Department of Internal Medicine, Showa University, Yokohama, Japan.
Shishido
K
K
Koshikawa
S
S
D000328:Adult; D000368:Aged; D000469:Alkaline Phosphatase / Q000378:metabolism; D001777:Blood Coagulation / Q000187:drug effects; D001792:Blood Platelets / Q000166:cytology / Q000187:drug effects; D002452:Cell Count; D004912:Erythrocytes / Q000166:cytology / Q000187:drug effects; D005260:Female; D016179:Granulocyte Colony-Stimulating Factor / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics / Q000494:pharmacology / Q000627:therapeutic use*; D006207:Half-Life; D006801:Humans; D007262:Infusions, Intravenous; D007676:Kidney Failure, Chronic / Q000188:drug therapy*; D008297:Male; D008875:Middle Aged; D009504:Neutrophils / Q000166:cytology / Q000187:drug effects* / Q000201:enzymology; D011994:Recombinant Proteins / Q000493:pharmacokinetics / Q000494:pharmacology / Q000627:therapeutic use; D006435:Renal Dialysis; D013601:T-Lymphocytes / Q000166:cytology / Q000187:drug effects
D011994:Recombinant Proteins; D016179:Granulocyte Colony-Stimulating Factor; D000469:Alkaline Phosphatase