Torcitabine (b-L-2u-deoxycytidine) (L-dC) is the b-L-enantiomer of the natural nucleoside D-cytidine. The drug is currently under development by Idenix as an antiviral agent for the treatment of chronic hepatitis B virus infection. Torcitabine has poor oral bioavailability, but its 3u,5u-divaline ester (val-L-dC) and the 3u-monovaline ester, valtorcitabine dihydrochloride, have excellent oral bioavailability and consequently the torcitabine prodrug, valtorcitabine, has replaced torcitabine in clinical development.
Torcitabine and its prodrug, valtorcitabine, are investigational drugs being developed solely for the treatment of chronic HBV infection. Torcitabine itself has undergone preliminary phase I/II clinical trials in HBeAg-positive patients, initially as the 3u,5u-divalyl prodrug in escalating doses of 50, 100, 200, and 400 mg/day, but later as the more stable monovaline ester form, valtorcitabine dihydrochloride, and administered to four cohorts in doses of 300, 600, 900, and 1200 mg/ day for 28 days.
