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Oral and Intravenous Zidovudine Pharmacokinetics: The Effect of Granulocyte‐Macrophage Colony Stimulating Factor
Author(s) -
Aweeka Francesca T.,
Mak May,
AlUzri Amira,
Peter Katrin,
Dett Carmen,
Franco Jose,
Affrime Melton,
Guerciolini Roberto,
Cutler David L.,
Kahn James,
Gambertoglio John G.
Publication year - 1995
Publication title -
the journal of clinical pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.92
H-Index - 116
eISSN - 1552-4604
pISSN - 0091-2700
DOI - 10.1002/j.1552-4604.1995.tb04130.x
Subject(s) - pharmacokinetics , zidovudine , granulocyte colony stimulating factor , granulocyte macrophage colony stimulating factor , pharmacology , medicine , granulocyte macrophage colony stimulating factor receptor , macrophage colony stimulating factor , macrophage , immunology , human immunodeficiency virus (hiv) , cytokine , chemistry , chemotherapy , in vitro , viral disease , biochemistry
Combination therapy with zidovudine and recombinant human granulocyte‐macrophage colony stimulating factor (rHu GM‐CSF) may be warranted, owing to the bone marrow suppressive effects of zidovudine. A study of 16 patients, 8 of whom had acquired immune deficiency syndrome (AIDS) and 8 of whom were infected with human immunodeficiency virus (HIV) but were asymptomatic, was conducted. The effect of 4 days of rHU GM‐CSF versus placebo on intermittent zidovudine therapy (200 mg every 8 hours) was evaluated using a randomized, cross‐over study design. Pharmacokinetics of oral and intravenous zidovudine were determined on days 1 (oral), 3 (oral), and 4 (intravenous) of rHu‐GM‐CSF (placebo) administration. After intravenous dosing, zidovudine plasma clearance for placebo and rHu GM‐CSF averaged 1.4 ± 0.2 and 1.3 ± 0.2 L/hr/kg, respectively (P = 0.017), mean residence time averaged 1.5 ± 0.5 and 1.9 ± 0.6 hours, respectively (P = 0.012), and the steady‐state volume of distribution was 2.0 ± 0.7 and 2.3 ± 0.7 L/kg, respectively (P = 0.027) for the two treatment arms. Stratified data for patients with AIDS and those with asymptomatic HIV infection revealed no significant difference in plasma clearance or mean residence time between the two patient groups. These pharmacokinetic results indicate that dosage adjustments for zidovudine are not warranted when administered with rHu GM‐CSF owing to the small changes observed. However, the statistically significant increase in Vss suggests the possibility of enhanced zidovudine cellular uptake in the presence of rHu GM‐CSF.