Emtricitabine (FTC, Emtriva™). Emtricitabine (FTC) (5-fluoro-1-(2R,5S)-[2-(hydroxymethyl)-1,3-oxathiolan-5-yl]cytosine) is a synthetic nucleoside analogue with activity against HIV-1 reverse transcriptase. FTC is the negative (-) enantiomer of a thio analogue of cytidine, which differs from cytidine analogues in that it has a fluorine in the 5-position. FTC is phosphorylated by cellular enzymes to form the active intracellular metabolite, emtricitabine 5’-triphosphate (FTC-TP), which is a competitive inhibitor of HIV-1 RT and terminates the growing DNA chain. Pre-Clinical The antiretroviral activity of FTC has been shown to up to 10-fold greater than Epivir® (lamivudine, 3TC) against HIV‑1 clinical isolates in vitro using human peripheral blood mononuclear cells (PBMCs), macrophages and laboratory adapted T-cell lines (Xxxxxxxx, 1992, Xxxxxxxx, 2003). Furthermore, FTC is incorporated approximately 9-fold more efficiently into viral DNA than 3TC while being 24-fold less efficiently incorporated in human mitochondrial DNA polymerase [Xxxx, 1998; Xxxx, 1999; Xxxx, 2001]. FTC selects the M184V mutation less often and less rapidly in vitro during serial passage experiments in human PBMCs [Xxxxxxxx, 1993]. FTC is rapidly absorbed following oral administration, with peak plasma concentrations occurring within 1-2 hours of dosing and with good oral bioavailability (93%) [Xxxx, 2001; Xxxxxxxx, 2001]. FTC has a long plasma half-life (10 hours) such that steady state concentrations following 200 mg once-daily dosing are above the concentration needed to produce 90% inhibition (IC90) of HIV replication for more than 80 hours [Xxxx, 2001; Xxxxxxxx, 2001; Xxxx, 2002]. The intracellular half-life of the active moiety, FTC-TP, is even longer, 39 hours, supporting once-daily dosing [Xxxx et al., 2001, Xxxxxxxx et al., 2001, Xxxx, 2002]. In vivo, FTC produced a 1.9 log10 reduction in HIV-1 RNA when given as monotherapy to HIV-infected patients for two weeks [Xxxxxxxx, 2001]. When given as monotherapy to HIV-infected patients for 10 days, FTC 200 mg QD demonstrated significantly greater antiviral activity compared to 3TC 150 mg BID as determined by plasma HIV-1 RNA average area under the curve minus baseline (AAUCMB) (p<0.05) [Xxxxxxxx, 2003]. Clinical Experience Two phase III controlled studies (FTC-301A, and FTC-303) provide the most information concerning the safety and efficacy of FTC in HIV-1-infected adults treated for extended periods with combinations of ART [Xxxx et al., 2003].
