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Pharmacokinetics and safety of concentration-controlled oral zidovudine therapy
E P Acosta1, K Henry, L M Page
1College of Pharmacy, University of Minnesota Health Sciences Center, Minneapolis, USA.
Study Objective:
To evaluate the pharmacokinetics, safety, and feasibility of concentration-controlled oral zidovudine therapy.
Design:
Randomized, crossover, open-label study.
Setting:
University-affiliated general clinical research center.
Patients:
Eight individuals infected with the human immunodeficiency virus with CD4+ lymphocyte counts of 100 cells/microliter or greater.
Intervention:
During the 24-week study, patients received oral zidovudine regimens that consisted of a standard fixed dose of 500 mg/day and a concentration-controlled regimen designed to maintain a steady-state plasma concentration (Css) of 0.187 +/- 0.04 mg/L (0.7 +/- 0.14 microM).
Measurements And Main Results:
The mean Css during standard therapy was 0.170 +/- 0.024 mg/L versus 0.205 +/- 0.021 mg/L with the concentration-controlled regimen (p = 0.025). Respective mean changes in hemoglobin were -0.02 g/dl (range -0.9-0.9 g/dl) and -0.30 g/dl (range -1.5-0.4 g/dl, p = 0.67). The absolute neutrophil count decreased 0.90 x 10(9)/L during standard therapy and increased 0.40 x 10(9)/L during concentration-controlled therapy (p = 0.07). The regimens did not differ in toxicity.
Conclusion:
Concentration-controlled oral antiretroviral therapy with zidovudine is feasible and safe, and provides pharmacologic data to determine the regimen's virologic and immunologic benefits.