Limits...
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.

Show MeSH
Schematic of the dosing regimen and PK sample collection. BDQ, bedaquiline; RIF, rifampicin; RPT, rifapentine.
© Copyright Policy - creative-commons
Related In: Results  -  Collection

License
getmorefigures.php?uid=PMC4356204&req=5

DKU504F1: Schematic of the dosing regimen and PK sample collection. BDQ, bedaquiline; RIF, rifampicin; RPT, rifapentine.

Mentions: A Phase I, two-arm open-label trial (study number TMC207-CL002) with a two-period, single-sequence design was performed to assess the PK interaction between bedaquiline and rifampicin (Arm 1) or rifapentine (Arm 2) (Figure 1). Healthy volunteers received a single 400 mg dose of bedaquiline on Day 1 followed by PK sampling (Days 1–14). On Day 20, Arm 1 participants started 600 mg rifampicin daily and Arm 2 participants started rifapentine 600 mg daily. On Day 29, a second 400 mg dose of bedaquiline was given to all study participants, again followed by 14 days of PK sampling (Days 29–43). Rifamycin dosing continued throughout the PK sampling period. Blood samples were collected pre-dose and at 1, 2, 3, 4, 5, 6, 8, 12 and 24 h and thereafter every 24th hour until 336 h after each bedaquiline dose and additionally just before the start of the rifamycin administration on Day 20. All clinical research was conducted in accordance with good clinical practice and with local ethics legislation; written informed consent was given by all participants.Figure 1.


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)

Schematic of the dosing regimen and PK sample collection. BDQ, bedaquiline; RIF, rifampicin; RPT, rifapentine.
© Copyright Policy - creative-commons
Related In: Results  -  Collection

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

DKU504F1: Schematic of the dosing regimen and PK sample collection. BDQ, bedaquiline; RIF, rifampicin; RPT, rifapentine.
Mentions: A Phase I, two-arm open-label trial (study number TMC207-CL002) with a two-period, single-sequence design was performed to assess the PK interaction between bedaquiline and rifampicin (Arm 1) or rifapentine (Arm 2) (Figure 1). Healthy volunteers received a single 400 mg dose of bedaquiline on Day 1 followed by PK sampling (Days 1–14). On Day 20, Arm 1 participants started 600 mg rifampicin daily and Arm 2 participants started rifapentine 600 mg daily. On Day 29, a second 400 mg dose of bedaquiline was given to all study participants, again followed by 14 days of PK sampling (Days 29–43). Rifamycin dosing continued throughout the PK sampling period. Blood samples were collected pre-dose and at 1, 2, 3, 4, 5, 6, 8, 12 and 24 h and thereafter every 24th hour until 336 h after each bedaquiline dose and additionally just before the start of the rifamycin administration on Day 20. All clinical research was conducted in accordance with good clinical practice and with local ethics legislation; written informed consent was given by all participants.Figure 1.

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