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Pharmacokinetics and pharmacodynamics of granulocyte-macrophage colony-stimulating factor and zidovudine in patients with AIDS and severe AIDS-related complex.

Abstract：

:Granulocytopenia is a complication of human immunodeficiency virus disease, as well as a toxic manifestation of zidovudine therapy. To evaluate pharmacokinetic and pharmacodynamic relationships, 11 AIDS-AIDS-related complex patients who had developed zidovudine-associated granulocytopenia (mean absolute neutrophil count, 1,077/mm3) were examined after addition of granulocyte-macrophage colony-stimulating factor (GM-CSF) to zidovudine. GM-CSF was administered as a daily (1.0 or 0.3 micrograms/kg) or every-other-day (0.3 micrograms/kg) subcutaneous dose over a 28-day period. Zidovudine was continued at the same daily dosage as was previously being administered. Of 11 patients, 7 (1.0 micrograms/kg, n = 5; 0.3 micrograms/kg, n = 2) had a pharmacologic response to GM-CSF with an increase to a mean absolute neutrophil count of 3,189 cells per mm3 at 4 weeks (P < 0.05). The peak concentration of GM-CSF in plasma ranged from 11.5 to 84.4 pg/ml, and the time to peak ranged from 1 to 3 h. No correlation between GM-CSF disposition and hematologic response was noted. A decreased plasma zidovudine-glucuronide/zidovudine ratio was noted after 1 week of GM-CSF, and an increase in the area under the plasma concentration-versus-time curve for zidovudine was found in three patients after 4 weeks. Low doses of GM-CSF can raise the granulocyte count in patients with zidovudine-induced neutropenia. The use of GM-CSF and zidovudine may represent a viable treatment option for persons with human immunodeficiency virus infection who develop neutropenia while receiving zidovudine but do not tolerate alternative nucleoside analogs. Further studies are needed to assess the complex interaction between these two agents.

journal_name

Antimicrob Agents Chemother

journal_title

Antimicrobial agents and chemotherapy

authors

Hewitt RG,Morse GD,Lawrence WD,Maliszewski ML,Santora J,Bartos L,Bonnem E,Poiesz B

doi

10.1128/aac.37.3.512

subject

Has Abstract

pub_date

1993-03-01 00:00:00

pages

512-22

issue

eissn

0066-4804

issn

1098-6596

journal_volume

pub_type

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Pharmacokinetics and pharmacodynamics of granulocyte-macrophage colony-stimulating factor and zidovudine in patients with AIDS and severe AIDS-related complex.