AIDS (London, England) · 2025
Assessment of the steady-state drug-drug interactions between dolutegravir and ritonavir-boosted darunavir in adolescents.
СтатьяКлиническое исследование II фазыКлиническое исследование III фазыНазвание и аннотация: Перевод в очереди
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Abdalla Seef, Compagnucci Alexandra, Bamford Alasdair, Chan Man K, Ramos José T, Riault Yoann, Saidi Yacine, Constant Valentin, Nguyen Thao-Nguyen, Giaquinto Carlo, Tréluyer Jean-Marc, Cressey Tim R, Hirt Déborah, the SMILE study group
Аннотация
OBJECTIVES: DTG is primarily metabolized by the UDP-glycosyltransferase (UGT) 1A1, and to a lesser extent by the cytochrome P450 (CYP) 3A4. Co-administration of DRV/r has been reported to decrease DTG plasma concentrations. Our aim was to distinguish the extent of the drug-drug interactions between DRV/r and DTG, and to evaluate the consequences of this interaction, in adolescents at steady state.
DESIGN: SMILE (PENTA 17-ANRS152) was a phase II/III trial assessing the safety and efficacy of once-daily dual therapy, using dolutegravir (DTG) combined with ritonavir-boosted darunavir (DRV/r), in virologically suppressed adolescents aged 12 years and older.
METHODS: A joint population pharmacokinetic model for DTG and DRV/r was developed with prior individual drug models (involving unbound and total concentrations) using SMILE data.
RESULTS: Unbound DRV exposure, integrated as a power function on unbound DTG clearance best described DRV/r inhibition of DTG elimination. Nevertheless, no interaction was identified between DRV/r and total DTG clearance. Moreover, the influence of unbound DRV exposures to predict unbound DTG concentrations was relatively small.
CONCLUSION: Administration of DRV/r 800/100 mg and DTG 50 mg once daily provides adequate concentrations and exposures with no clinically relevant drug-drug interactions at steady-state.
DESIGN: SMILE (PENTA 17-ANRS152) was a phase II/III trial assessing the safety and efficacy of once-daily dual therapy, using dolutegravir (DTG) combined with ritonavir-boosted darunavir (DRV/r), in virologically suppressed adolescents aged 12 years and older.
METHODS: A joint population pharmacokinetic model for DTG and DRV/r was developed with prior individual drug models (involving unbound and total concentrations) using SMILE data.
RESULTS: Unbound DRV exposure, integrated as a power function on unbound DTG clearance best described DRV/r inhibition of DTG elimination. Nevertheless, no interaction was identified between DRV/r and total DTG clearance. Moreover, the influence of unbound DRV exposures to predict unbound DTG concentrations was relatively small.
CONCLUSION: Administration of DRV/r 800/100 mg and DTG 50 mg once daily provides adequate concentrations and exposures with no clinically relevant drug-drug interactions at steady-state.