Rilpivirine (hydrochloride)

Rilpivirine (R278474) hydrochloride is a potent and specific diarylpyrimidine (DAPY) non-nucleoside reverse transcriptase inhibitor (NNRTI). Rilpivirine hydrochloride has high antiviral activity against wild-type HIV (EC₅₀=0.4 nM) and mutant viruses (EC₅₀=0.1-2.0 nM). Rilpivirine hydrochloride has a high genetic barrier to resistance development of HIV^[1][2]. IC50 & Target:IC50: 20±10 μM (MMP)^[1] Ki: 1.5±0.27 nM (MMPs)^[1] In Vitro:R278474 is active against wild-type HIV-1 (EC₅₀=0.4 nM) and all single and double mutants tested (EC₅₀=0.1-2.0 nM)^[1].
R278474 (10-5000 nM; 30 d) does not observe the sign of wild-type HIV-1 breakthrough at 1 μM within 30 days^[1].
R278474 inhibits 81% of clinical isolates (about 1200 recombinant clinical isolates) at a 50% inhibitory concentration (EC₅₀) less than 1 nM, and inhibits 94% at EC₅₀ less than 10 nM^[1].
TMC278 shows subnanomolar EC₅₀s against wild-type HIV-1 group M isolates (0.07-1.01 nM)^[2]. In Vivo:R278474 (10-160 mg/kg; p.o. for 1 month) does not produce abnormal effects in rat, apart from liver weight increase and species-specific thyroid hypertrophy, both at the higher dose levels^[1].
R278474 (i.v.) exhibits elimination half-life ranges from 4.4 h in rat to 31 h in dog, and exposure (AUC_inf) amounts to 3.1 μg h/mL (4 mg/kg) in rat, 8.7 μg h/mL (1.25 mg/kg) in dog, 1.4 μg h/mL (1.25 mg/ kg) in monkey, and 44 μg h/mL (1.25 mg/kg) in rabbit^[1].
R278474 (p.o.) exhibits half-life ranges between 2.8 h in rat and 39 h in dog, and oral bioavailability of 32% and 31% in rat and dog^[1].