Impact of dosing schedule upon suppression of a retrovirus in a murine model of AIDS encephalopathy.
We studied the impact of zidovudine (AZT) in Cas-Br-M murine leukemia virus-infected NFS-N mice after administration by once-daily bolus or continuous infusion. While higher peak concentrations of AZT were achieved by once-daily dosing, continuous AZT infusion at 25 micrograms/h maintained levels > 1 microM in plasma and > 0.2 microM in the brain. Continuous infusion provided significantly better viral inhibition, even though total doses were only one-third that of the once-daily therapy group.
Bilello
J A
JA
Department of Microbiology and Immunology, University of Maryland Cancer Center, Baltimore.
Eiseman
J L
JL
Standiford
H C
HC
Drusano
G L
GL
D015526:AIDS Dementia Complex / Q000188:drug therapy* / Q000382:microbiology; D000818:Animals; D001921:Brain / Q000378:metabolism; D002851:Chromatography, High Pressure Liquid; D004591:Electrophoresis, Polyacrylamide Gel; D005260:Female; D006207:Half-Life; D015151:Immunoblotting; D051379:Mice; D008815:Mice, Inbred Strains; D011247:Pregnancy; D012190:Retroviridae; D012192:Retroviridae Infections / Q000188:drug therapy* / Q000382:microbiology; D013154:Spleen / Q000382:microbiology; D015215:Zidovudine / Q000008:administration & dosage* / Q000493:pharmacokinetics / Q000627:therapeutic use*
D015215:Zidovudine