Pharmacokinetics of recombinant human granulocyte-macrophage colony-stimulating factor: The effects of zidovudine

Francesco T. Aweeka, Mae Kwong, May Mak, Almira Al-Uzri, Mel Affrime, David Cutler, James Kahn, John G. Gambertoglio

Research output: Contribution to journalArticle

1 Scopus citations

Abstract

Recombinant human granulocyte-macrophage colony-stimulating factor (rHu GM-CSF) enhances bone marrow production of and stimulates granulocytes, macrophages, and eosinophils. Granulocyte-macrophage colony-stimulating factor may be used concomitantly with zidovudine in human immunodeficiency virus (HIV)-positive patients to minimize zidovudine-associated neutropenia. This open-label, randomized, placebo-controlled study was performed to evaluate the pharmacokinetic disposition of rHu GM-CSF in HIV-positive, asymptomatic patients in the absence and presence of concomitant zidovudine administration. Eight participants received rHu GM-CSF (5 μg/kg subcutaneously) daily for 4 days in combination with placebo or zidovudine (200 mg orally every 8 hours) in a randomized, crossover fashion, with each study period separated by a 3-day washout phase. Pharmacokinetic blood sampling was performed over 16 hours on days 1 and 4 of both treatment periods, and subsequent analysis of serum was performed using an enzyme-linked immunosorbent assay. Pharmacokinetic results of rHu GM-CSF at steady state (days 4 of periods I and II) in the absence (placebo) and presence of zidovudine included apparent total body clearance, half-life, and apparent volume of distribution, all of which were not significantly altered with concomitant administration of zidovudine. Mean pharmacokinetic results of rHu GM-CSF after the first dose (days 1 of periods I and II) were similar to steady-state values; however, total body clearance was significantly increased at steady state compared with the results of the first dose. Concurrent administration of zidovudine does not influence the pharmacokinetic disposition of rHu GM-CSF after single or multiple doses.

Original languageEnglish (US)
Pages (from-to)1107-1113
Number of pages7
JournalJournal of Clinical Pharmacology
Volume36
Issue number12
DOIs
StatePublished - Jan 1 1996

ASJC Scopus subject areas

  • Pharmacology
  • Pharmacology (medical)

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