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Nasal absorption of 2',3'-didehydro-3'-deoxythymidine (D4T) and its esters (5'-acetyl D4T: C2-D4T and 5'-hemisuccinyl D4T: Suc-D4T) was investigated in rats. Bioavailability of D4T following intranasal (i.n.) administration was 98.0%, and the elimination from plasma was as rapid as that following intravenous administration of D4T. There seemed to be complete and rapid absorption of D4T from the nasal cavity. The plasma concentration-time profile of D4T following i.n. administration of C2-D4T was almost the same as that after administration of D4T itself. This suggests that C2-D4T was rapidly absorbed from the nasal cavity, and that some amount of dosing C2-D4T was hydrolyzed to D4T before entering the systemic circulation. In contrast, Suc-D4T showed slower absorption in the i.n. administration, and the plasma D4T level was maintained for a long period.

Nasal Absorption of 2',3'-Didehydro-3'-deoxythymidine (D4T) and Its Esters in Rats.