Brain, blood, and cerebrospinal fluid distribution of a zidovudine chemical delivery system in rabbits.
Improved brain delivery of zidovudine (AZT) was shown to occur after iv dosing of a chemical delivery system (CDS) for the modified deoxynucleoside. Specifically, administration of a 25-mg/kg dose of 5'-[(1-methyl-1,4-dihydropyridin-3-yl)carbonyl]-3'-azido-3'-deoxyt hymidine (AZT-CDS) generated higher and more sustained levels of AZT in brain tissue of rabbits than did dosing with AZT itself. The significant increase in the area under the AZT brain concentration-time curve occurred with lower AZT present in the systemic circulation and with similar AZT levels in cerebrospinal fluid. These results, as well as previously published reports examining AZT-CDS in mice, rats, and dogs, indicate that this delivery system may be beneficial in the treatment of AIDS-related encephalopathy.
Brewster
M E
ME
Center for Drug Design and Delivery, College of Pharmacy, University of Florida, Gainesville 32510.
Anderson
W
W
Bodor
N
N
D000818:Animals; D001812:Blood-Brain Barrier; D001921:Brain / Q000378:metabolism*; D004095:Dihydropyridines / Q000493:pharmacokinetics*; D004337:Drug Carriers; D008297:Male; D011355:Prodrugs / Q000493:pharmacokinetics*; D011817:Rabbits; D015215:Zidovudine / Q000031:analogs & derivatives* / Q000493:pharmacokinetics
D004095:Dihydropyridines; D004337:Drug Carriers; D011355:Prodrugs; C056534:5'-(1,4-dihydro-1-methyl-3-pyridinylcarbonyl)-3'-azido-3'-deoxythymidine; D015215:Zidovudine