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Rifampicin and rifapentine significantly reduce concentrations of bedaquiline, a new anti-TB drug.

Svensson EM, Murray S, Karlsson MO, Dooley KE - J. Antimicrob. Chemother. (2014)

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.

View Article: PubMed Central - PubMed

Affiliation: Department of Pharmaceutical Biosciences, Uppsala University, PO Box 591, 751 24 Uppsala, Sweden elin.svensson@farmbio.uu.se.

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PK profiles for bedaquiline (continuous lines) and M2 (broken lines) during the first 4 weeks of bedaquiline treatment alone (black), with rifampicin (dark grey) or with rifapentine (light grey). Profiles are representative of a 70 kg healthy volunteer. The concentrations are depicted on a logarithmic scale. BDQ, bedaquiline; RIF, rifampicin; RPT, rifapentine.
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DKU504F3: PK profiles for bedaquiline (continuous lines) and M2 (broken lines) during the first 4 weeks of bedaquiline treatment alone (black), with rifampicin (dark grey) or with rifapentine (light grey). Profiles are representative of a 70 kg healthy volunteer. The concentrations are depicted on a logarithmic scale. BDQ, bedaquiline; RIF, rifampicin; RPT, rifapentine.

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.


Rifampicin and rifapentine significantly reduce concentrations of bedaquiline, a new anti-TB drug.

Svensson EM, Murray S, Karlsson MO, Dooley KE - J. Antimicrob. Chemother. (2014)

PK profiles for bedaquiline (continuous lines) and M2 (broken lines) during the first 4 weeks of bedaquiline treatment alone (black), with rifampicin (dark grey) or with rifapentine (light grey). Profiles are representative of a 70 kg healthy volunteer. The concentrations are depicted on a logarithmic scale. BDQ, bedaquiline; RIF, rifampicin; RPT, rifapentine.
© Copyright Policy - creative-commons
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4356204&req=5

DKU504F3: PK profiles for bedaquiline (continuous lines) and M2 (broken lines) during the first 4 weeks of bedaquiline treatment alone (black), with rifampicin (dark grey) or with rifapentine (light grey). Profiles are representative of a 70 kg healthy volunteer. The concentrations are depicted on a logarithmic scale. BDQ, bedaquiline; RIF, rifampicin; RPT, rifapentine.
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.

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.

View Article: PubMed Central - PubMed

Affiliation: Department of Pharmaceutical Biosciences, Uppsala University, PO Box 591, 751 24 Uppsala, Sweden elin.svensson@farmbio.uu.se.

Show MeSH