BACKGROUND: Rilpivirine and efavirenz share metabolic pathways (CYP3A), potentially leading to drug-drug interactions. We report the pharmacokinetics, ex vivo antiviral activity and safety of rilpivirine, following efavirenz treatment. METHODS: HIV-negative adults received in fixed sequence: treatment A (rilpivirine 25 mg once daily for 14 days, followed by a washout), treatment B (efavirenz 600 mg once daily for 14 days), immediately followed by treatment C (rilpivirine 25 mg once daily for 28 days). Rilpivirine pharmacokinetic profiles were determined on days 1 and 14 of treatment A and days 1, 14, 21 and 28 of treatment C. Ex vivo antiviral activity was measured in treatments A and C using an exploratory assay. Safety was evaluated throughout. RESULTS: From days 1 to 21, higher mean rilpivirine exposure was observed with treatment A compared with treatment C. The area under the concentration-time curve (AUC(24 h)) least squares (LS) means ratio (90% CI) for treatment C versus treatment A was 0.54 (0.46, 0.64; Day 1), 0.82 (0.75, 0.89; Day 14) and 0.84 (0.74, 0.94; Day 21). By day 28 of treatment C, the main rilpivirine pharmacokinetic parameters were similar to day 14 of treatment A (AUC(24 h) LS means ratio [90% CI], 0.91 [0.82, 1.01]), except for the minimum plasma concentration. At each time point in treatment C, samples of >80% of subjects demonstrated similar ex vivo antiviral activity compared with treatment A. All adverse events were grade 1 or 2. CONCLUSIONS: These results provide useful information supporting a clinical study evaluating HIV-1-positive subjects switching from efavirenz to rilpivirine.
BACKGROUND:Rilpivirine and efavirenz share metabolic pathways (CYP3A), potentially leading to drug-drug interactions. We report the pharmacokinetics, ex vivo antiviral activity and safety of rilpivirine, following efavirenz treatment. METHODS: HIV-negative adults received in fixed sequence: treatment A (rilpivirine 25 mg once daily for 14 days, followed by a washout), treatment B (efavirenz 600 mg once daily for 14 days), immediately followed by treatment C (rilpivirine 25 mg once daily for 28 days). Rilpivirine pharmacokinetic profiles were determined on days 1 and 14 of treatment A and days 1, 14, 21 and 28 of treatment C. Ex vivo antiviral activity was measured in treatments A and C using an exploratory assay. Safety was evaluated throughout. RESULTS: From days 1 to 21, higher mean rilpivirine exposure was observed with treatment A compared with treatment C. The area under the concentration-time curve (AUC(24 h)) least squares (LS) means ratio (90% CI) for treatment C versus treatment A was 0.54 (0.46, 0.64; Day 1), 0.82 (0.75, 0.89; Day 14) and 0.84 (0.74, 0.94; Day 21). By day 28 of treatment C, the main rilpivirine pharmacokinetic parameters were similar to day 14 of treatment A (AUC(24 h) LS means ratio [90% CI], 0.91 [0.82, 1.01]), except for the minimum plasma concentration. At each time point in treatment C, samples of >80% of subjects demonstrated similar ex vivo antiviral activity compared with treatment A. All adverse events were grade 1 or 2. CONCLUSIONS: These results provide useful information supporting a clinical study evaluating HIV-1-positive subjects switching from efavirenz to rilpivirine.
Authors: Anna H Tran; Brookie M Best; Alice Stek; Jiajia Wang; Edmund V Capparelli; Sandra K Burchett; Regis Kreitchmann; Kittipong Rungruengthanakit; Kathleen George; Tim R Cressey; Nahida Chakhtoura; Elizabeth Smith; David E Shapiro; Mark Mirochnick Journal: J Acquir Immune Defic Syndr Date: 2016-07-01 Impact factor: 3.731
Authors: Julieta Díaz-Delfín; Pere Domingo; Maria Gracia Mateo; Maria Del Mar Gutierrez; Joan Carles Domingo; Marta Giralt; Francesc Villarroya Journal: Antimicrob Agents Chemother Date: 2012-03-19 Impact factor: 5.191
Authors: Ka Lai Yee; Rosa I Sanchez; Patrice Auger; Rachael Liu; Li Fan; Ilias Triantafyllou; Ming-Tain Lai; Mike Di Spirito; Marian Iwamoto; Sauzanne G Khalilieh Journal: Antimicrob Agents Chemother Date: 2017-01-24 Impact factor: 5.191
Authors: Sauzanne G Khalilieh; Ka Lai Yee; Rosa I Sanchez; Li Fan; Matt S Anderson; Monali Sura; Tine Laethem; Scott Rasmussen; Luc van Bortel; Griet van Lancker; Marian Iwamoto Journal: Antimicrob Agents Chemother Date: 2019-04-25 Impact factor: 5.191