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J Infect Dis. 1996 Sep;174(3):490-9.

A systemic and cellular model for zidovudine plasma concentrations and intracellular phosphorylation in patients.

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1
Department of Pharmaceutical Sciences, St. Jude Children's Research Hospital, Memphis, Tennessee 38105, USA.

Abstract

In a pharmacokinetic model for the systemic and cellular disposition of zidovudine in patients, serial measurements of plasma zidovudine and intracellular metabolites were used to simultaneously characterize systemic pharmacokinetics and intracellular phosphorylation in 6 human immunodeficiency virus-infected patients. First-order processes are sufficient to describe zidovudine monophosphate kinetics in peripheral blood mononuclear cells (PBMC), and the pharmacokinetic model provided reliable parameter estimates for each subject. The amount of zidovudine monophosphate in PBMC was inversely correlated with plasma zidovudine concentrations, and patients with higher systemic clearance had less intracellular zidovudine monophosphate. Zidovudine triphosphate values were measurable but not different at each time point. Lower lymphocyte counts were associated with higher intracellular zidovudine monophosphate but lower zidovudine triphosphate. The pharmacokinetic model proposed provides a quantitative link between systemic zidovudine concentrations and zidovudine monophosphate in PBMC from patients that will be useful in evaluating alternative therapeutic strategies.

PMID:
8769605
[Indexed for MEDLINE]

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