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'-deoxythymidine (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.