title: Comparative pharmacokinetics of zidovudine in healthy volunteers and in patients with AIDS with and without hepatic disease.
abstract: To understand whether disease caused by the human immunodeficiency virus (HIV) affects zidovudine disposition, we compared the drug's pharmacokinetics in six healthy volunteers; six persons with the acquired immunodeficiency syndrome (AIDS) and no evidence of gastrointestinal (nausea, vomiting, diarrhea), renal (elevated blood urea nitrogen, serum creatinine), or hepatic (elevated liver function tests) disease; and three patients with AIDS and hepatic disease. After a single oral dose of zidovudine, serial blood samples were analyzed for drug concentration by radioimmunoassay. A one-compartment oral absorption model was fit to the concentration-time data. The absorption rate constant (4.05 vs 2.11 hr-1) and time to maximum concentration (0.61 vs 1.03 hr) were significantly different in healthy volunteers versus patients with AIDS without hepatic disease. Differences in half-life, oral clearance, and area under the curve were not statistically significant. In the three patients with AIDS plus hepatic disease, clearance was reduced an average of 63%, and area under the curve was increased by a factor of 2.3. These comparative pharmacokinetic data do not support profound differences between zidovudine's disposition in healthy volunteers and individuals with AIDS; however, the differences and trends that were observed may represent an effect of HIV disease. Although the presence of hepatic disease clearly indicates a need to modify individual dosages, these pharmacokinetic data may have more generalized implications for zidovudine dosing as the relationships between drug concentration and therapeutic or toxic effects are clarified.
authors: Department of Pharmacy Practice, College of Pharmacy, University of Minnesota, Minneapolis 55455.
authors: C V
authors: CV
authors: Fletcher
authors: F S
authors: FS
authors: Rhame
authors: C C
authors: CC
authors: Beatty
authors: M
authors: M
authors: Simpson
authors: H H
authors: HH
authors: Balfour
mesh_terms: D000042:Absorption; D000163:Acquired Immunodeficiency Syndrome / Q000150:complications / Q000378:metabolism*; D000284:Administration, Oral; D006801:Humans; D008107:Liver Diseases / Q000150:complications / Q000378:metabolism*; D008111:Liver Function Tests; D008657:Metabolic Clearance Rate; D008954:Models, Biological; D011863:Radioimmunoassay; D015215:Zidovudine / Q000008:administration & dosage / Q000493:pharmacokinetics*
chemical_list: D015215:Zidovudine