Rifampicin and rifapentine significantly reduce concentrations of bedaquiline, a new anti-TB drug.
Bottom Line: Pharmacokinetic analyses were performed using non-linear mixed-effects modelling.Average steady-state concentrations of bedaquiline and M2 are predicted to decrease by 79% and 75% when given with rifampicin or rifapentine, respectively.Rifamycin antibiotics reduce bedaquiline concentrations substantially.
Affiliation: Department of Pharmaceutical Biosciences, Uppsala University, PO Box 591, 751 24 Uppsala, Sweden firstname.lastname@example.org.Show MeSH
Mentions: The interaction with rifampicin during continuous co-administration is predicted to decrease the Css,avg of bedaquiline and M2 to 21% (RSE 9.10%) of the levels expected when bedaquiline is administered alone. The interaction with rifapentine is only slightly less strong and would decrease the Css,avg of bedaquiline and M2 to 25% (RSE 5.0%). Typical bedaquiline and M2 concentration–time profiles (for a 70 kg healthy volunteer) during the first 4 weeks of bedaquiline administration alone or with rifamycin co-administration were simulated (Figure 3). Results of simulations of a dose adjustment to mitigate the interaction effect are shown in Figure 4 and are further explained in the Discussion section.Figure 3.
Affiliation: Department of Pharmaceutical Biosciences, Uppsala University, PO Box 591, 751 24 Uppsala, Sweden email@example.com.