Background:

Didanosine(Videx) is a reverse transcriptase inhibitor with an IC50 of 0.49 μM.Target: NRTIs; HIVDidanosine is a dideoxynucleoside compound in which the 3'-hydroxy group on the sugar moiety has been replaced by a hydrogen. This modification prevents the formation of phosphodiester linkages which are needed for the completion of nucleic acid chains. Didanosine is a potent inhibitor of HIV replication, acting as a chain-terminator of viral DNA by binding to reverse transcriptase. Didanosine demonstrated linear pharmacokinetic behavior over the dose ranges of 0.4 to 16.5 mg/kg intravenously and 0.8 to 10.2 mg/kg orally. Bioavailability of didanosine when administered as a solution with an antacid was approximately 43% for doses from 0.8 to 10.2 mg/kg in patients with AIDS and advanced AIDS-related complex. Bioavailability of didanosine from the citrate-phosphate-buffered solution, the formulation currently used in phase II and expanded access studies, was comparable to the formulation used in the phase I trials [1]. ddI might be responsible for fulminant hepatitis in all three AIDS patients. This toxic effect may be added to the list of potential adverse events occurring during ddI therapy [2].

参考文献:
[1]. Knupp, C.A., et al., Pharmacokinetics of didanosine in patients with acquired immunodeficiency syndrome or acquired immunodeficiency syndrome-related complex. Clin Pharmacol Ther, 1991. 49(5): p. 523-35.
[2]. Bissuel, F., et al., Fulminant hepatitis with severe lactate acidosis in HIV-infected patients on didanosine therapy. J Intern Med, 1994. 235(4): p. 367-71.