Clinical pharmacokinetics of zidovudine. An update.
The battle against the acquired immune deficiency syndrome (AIDS) is now into its second decade, and substantial advancements have been made in our understanding of the complex life cycle of, and the immunopathology associated with, human immunodeficiency virus (HIV) infection, as well as of the drugs used to modify the course of disease. Zidovudine was the first agent approved for treatment of HIV disease, and since its widespread availability in 1987 the pharmacokinetic disposition and clinical effects of zidovudine have been extensively evaluated. This article reviews the absorption, distribution, metabolism and elimination characteristics of zidovudine, focusing on more recent information. In addition, factors that may or may not affect zidovudine disposition are discussed. These include selected drug interactions and concomitant disease states such as renal and hepatic insufficiency. Issues such as bodyweight normalisation, maternal-fetal transfer, pregnancy and intracellular phosphorylation are discussed in relation to the pharmacokinetics and clinical efficacy of zidovudine. Finally, information regarding the clinical pharmacodynamics of zidovudine is presented. This includes possible relationships between zidovudine pharmacokinetics and markers of efficacy and toxicity, and the significance of linking pharmacokinetic and pharmacodynamic information.
Acosta
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Department of Pharmacy Practice, University of Minnesota, Minneapolis, USA.
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Fletcher
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D000367:Age Factors; D000998:Antiviral Agents / Q000493:pharmacokinetics*; D001682:Biological Availability; D004347:Drug Interactions; D015658:HIV Infections / Q000378:metabolism*; D006801:Humans; D014018:Tissue Distribution; D015215:Zidovudine / Q000493:pharmacokinetics*
D000998:Antiviral Agents; D015215:Zidovudine