Pharmacokinetics of Recombinant Human Granulocyte‐Macrophage Colony‐Stimulating Factor: The Effects of Zidovudine

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 micrograms/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.