Pharmacokinetics and pharmacodynamics of pegfilgrastim in subjects with various degrees of renal function.
A phase I study was conducted to evaluate the effects of renal function on the pharmacokinetics and pharmacodynamics (absolute neutrophil count [ANC]) of pegfilgrastim in nonneutropenic subjects. Thirty subjects categorized into 5 renal function groups (normal, mildly impaired, moderately impaired, severely impaired, and end-stage renal disease) received 1 subcutaneous injection of pegfilgrastim at 6 mg. The ANC profiles after pegfilgrastim administration were similar across different renal function groups. No discernable correlation between pharmacokinetic parameter values and degree of renal impairment was observed; the mean values ranged from 147 to 201 ng/mL for C(max) and from 7469 to 8513 ng x h/mL for AUC. Results suggest that the kidney has no important role in the elimination of pegfilgrastim. Therefore, no dosage adjustment for renal impairment is indicated for pegfilgrastim.
Yang
Bing-Bing
BB
Amgen Inc, Thousand Oaks, CA 91320, USA. byang@amgen.com
Kido
Anna
A
Salfi
Margaret
M
Swan
Suzanne
S
Sullivan
John T
JT
D000328:Adult; D000368:Aged; D005260:Female; D000069585:Filgrastim; D016179:Granulocyte Colony-Stimulating Factor / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics*; D006801:Humans; D007279:Injections, Subcutaneous; D007674:Kidney Diseases / Q000097:blood / Q000378:metabolism* / Q000628:therapy; D007958:Leukocyte Count; D008297:Male; D008875:Middle Aged; D009504:Neutrophils / Q000187:drug effects*; D011092:Polyethylene Glycols; D011994:Recombinant Proteins; D006435:Renal Dialysis; D012720:Severity of Illness Index
D011994:Recombinant Proteins; D016179:Granulocyte Colony-Stimulating Factor; C455861:pegfilgrastim; D011092:Polyethylene Glycols; D000069585:Filgrastim