Pharmacokinetics and safety of concentration-controlled oral zidovudine therapy

Abstract

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.