Apricitabine

Apricitabine (SPD754; AVX754), the (-) enantiomer of 2′-deoxy-3′-oxa-4′-thiocytidine (dOTC), is a highly selective and orally active HIV-1 reverse transcriptase (RT) inhibitor (K_i=0.08 μM), as well as inhibits DNA polymerases α, β, and γ with K_i value of 300 μM, 12 μM, and 112.25 μM, respectively^[1]. Apricitabine (SPD754; AVX754) shows promising antiretroviral efficacy, good tolerability and a low propensity for resistance selection in antiretroviral-naive HIV infection^{[2]. In Vitro: Apricitabine (SPD754; AVX754) is against clinical isolates of HIV-1 in cultured PBMCs with IC₅₀ values of 0.2 μM, 1.45 μM, 2.2 μM and 2.4 μM for HIV-1RF, Wild type, 3TC resistant, 3TC and AZT resistant, respectively[1].
Apricitabine (SPD754; AVX754) has antiviral activities agsinst HIV-1 clinical isolates resistant to nucleoside reverse transcriptase inhibitors in MT-4 cells, exhibits Mean IC₅₀ values of 20 μM, 25 μM, 30 μM,21 μM,55 μM,32 μM and 71 μM for HIV-1IIIB,Wild-type (control), Zidovudine-resistant, Lamivudine-resistant, Zidovudine-resistant/lamivudine-resistant, Abacavir-resistant and Stavudine-resistant viruses,respectively[2].
In Vivo: Apricitabine (SPD754; AVX754) (oral adminstation; 10 mg/kg; once a day) exhibits a good oral bioavailability of 68% for males and 69.4% for females rats. And the T_1/2, AUC_0–∞, T_max, C_max are 62.2 mins, 157.4 μg/min/ml and 37.3 mins, 1.16 μg/ml in female rats[1].
Apricitabine (SPD754; AVX754) (intravenous injection; 10 mg/kg; once a day) exhibits the T_1/2, AUC_0–∞ values of 12.7 mins, 226.9 μg/min/ml in female rats[1].}