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In an attempt to develop a transdermal therapeutic system for 2', 3'-didehydro-3'-deoxythymidine (D4T) and its lipophilic prodrugs, percutaneous penetration of the drugs was examined in rat skin. The ability of penetration enhancers (Azone and l-menthol) to increase transdermal delivery of the drugs was evaluated in excised rat skin. Azone and l-menthol showed a significant enhancing effect on the penetration of D4T and its 5'-acetate (C2-D4T) at a concentration of 3 % in water. The penetration of 5'-octanoate (C8-D4T) was, however, hardly observed even in the presence of the enhancers. A D4T suspension containing l-menthol (3 %) was applied on rat abdominal skin, and the plasma concentration was measured. D4T was detected in plasma at 12 hours after the application, and a constant plasma concentration (1-3 μM ) was maintained for 8 hours

Percutaneous penetration of 2',3'-didehydro-3'-deoxythymidine. (D4T) and its ester prodrugs through rat skin.