Comparative pharmacokinetics of zidovudine in healthy volunteers and in patients with AIDS with and without hepatic disease.
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.
Fletcher
C V
CV
Department of Pharmacy Practice, College of Pharmacy, University of Minnesota, Minneapolis 55455.
Rhame
F S
FS
Beatty
C C
CC
Simpson
M
M
Balfour
H H
HH
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*
D015215:Zidovudine