77421-68-2Relevant articles and documents
Nasal absorption of 2',3'-didehydro-3'-deoxythymidine (D4T) and its esters in rats
Yajima, Toshiyuki,Hasegawa, Tetsuya,Juni, Kazuhiko,Saneyoshi, Mineo,Kawaguchi, Takeo
, p. 1234 - 1237 (1996)
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.
Process for preparing 5′-acetylstavudine
-
Page column 5, (2008/06/13)
The present invention relates to a process for preparing 5′-acetylstavudine, an intermediate which is useful in the preparation of 2′,3′-didehydro-3′-deoxythymidine, an active principle with antiviral action which is commonly known as stavudine (D4T).
Direct Transport of 2',3'-Didehydro-3'-deoxythymidine (D4T) and Its Ester Derivatives to the Cerebrospinal Fluid via the Nasal Mucous Membrane in Rats
Yajima, Toshiyuki,Juni, Kazuhiko,Saneyoshi, Mineo,Hasegawa, Tetsuya,Kawaguchi, Takeo
, p. 272 - 277 (2007/10/03)
We investigated the absorption and transport of 2',3'-didehydro-3'-deoxythymidine (D4T) and its ester prodrugs from the nasal cavity in rats. The absorption of D4T and its acetate (C2-D4T) was rapid and almost complete, although the hemi-succinate (Suc-D4T) was absorbed rather slowly; the plasma concentrations of the prodrug, Suc-D4T, and regenerated D4T remained unchanged throughout the experimental period (180 min). Concentrations in the cerebrospinal fluid (CSF) following intravenous (i.v.) and intranasal (i.n.) administration were also measured. After i.n. administration, drug concentrations were higher in the fraction derived from the subarachnoid space located close to the nasal mucosa than those in the fractions located far from the nasal cavity. This difference was not found following the i.v. administration of the drugs. Following nasal administration, the intact Suc-D4T was found in the CSF at a concentration higher than that of D4T, although transport of the intact prodrug to the CSF was not observed following i.v. adinistration. These results suggest that direct transport of the drugs from the nasal cavity to the CSF significantly contributes to the higher concentrations in CSF of D4T and/or its ester prodrugs, and indicate the possible value of nasal administration for the treatment of patients with AIDS dementia.