Plasma pharmacokinetics of high dose oral versus intravenous rifampicin in patients with tuberculous meningitis: a randomized controlled trial. Wasserman, S., Davis, A. G, Stek, C., Chirehwa, M., Botha, S., Daroowala, R., Bremer, M., Maxebengula, M., Koekemoer, S., Goliath, R., Jackson, A., Crede, T., Naude, J., Szymanski, P., Vallie, Y., Moosa, M. S, Wiesner, L., Black, J., Meintjes, G., Maartens, G., & Wilkinson, R. J Antimicrobial Agents and Chemotherapy, 65(8):e00140, American Society for Microbiology Journals, may, 2021. ![Plasma pharmacokinetics of high dose oral versus intravenous rifampicin in patients with tuberculous meningitis: a randomized controlled trial [link]](https://bibbase.org/img/filetypes/link.svg "link")
Paper doi abstract bibtex Background Higher doses of intravenous rifampicin may improve outcomes in tuberculous meningitis but is impractical in high burden settings. We hypothesized that plasma rifampicin exposures would be similar between oral 35 mg/kg and intravenous 20 mg/kg, which has been proposed for efficacy trials in tuberculous meningitis. Materials and methods We performed a randomized parallel group pharmacokinetic study nested within a clinical trial of intensified antimicrobial therapy for tuberculous meningitis. HIV-positive participants with tuberculous meningitis were recruited from South African hospitals and randomized to one of three rifampicin dosing groups: standard (oral 10 mg/kg), high dose (oral 35 mg/kg), and intravenous (intravenous 20 mg/kg). Intensive pharmacokinetic sampling was done on day 3. Data were described using non-compartmental analysis and exposures compared by geometric mean ratio (GMR). Results Forty-six participants underwent pharmacokinetic sampling (standard dose, n = 17; high dose oral, n= 15; intravenous, n = 14). Median CD4 count was 130 cells/mm3 (IQR 66 - 253). Rifampicin geometric mean AUC0-24 was 42.9 $μ$g˙h/mL (95% CI, 24.5 – 75.0) for standard dose; 295.2 $μ$g˙h/mL (95% CI, 189.9 – 458.8) for high dose oral; and 206.5 $μ$g˙h/mL (95% CI, 154.6 – 275.8) for intravenous administration. Rifampicin AUC0-24 GMR was 1.44 (90% CI, 0.84 - 2.21) and Cmax GMR was 0.89 (90% CI, 0.63 – 1.23) for high dose oral with respect to intravenous dosing. Conclusions Plasma rifampicin AUC0-24 was higher after an oral 35 mg/kg dose compared with intravenous administration at 20 mg/kg dose over the first few days of TB treatment. Findings support oral rifampicin dosing in future tuberculous meningitis trials.
@article{Wasserman2021a,
abstract = {Background Higher doses of intravenous rifampicin may improve outcomes in tuberculous meningitis but is impractical in high burden settings. We hypothesized that plasma rifampicin exposures would be similar between oral 35 mg/kg and intravenous 20 mg/kg, which has been proposed for efficacy trials in tuberculous meningitis. Materials and methods We performed a randomized parallel group pharmacokinetic study nested within a clinical trial of intensified antimicrobial therapy for tuberculous meningitis. HIV-positive participants with tuberculous meningitis were recruited from South African hospitals and randomized to one of three rifampicin dosing groups: standard (oral 10 mg/kg), high dose (oral 35 mg/kg), and intravenous (intravenous 20 mg/kg). Intensive pharmacokinetic sampling was done on day 3. Data were described using non-compartmental analysis and exposures compared by geometric mean ratio (GMR). Results Forty-six participants underwent pharmacokinetic sampling (standard dose, n = 17; high dose oral, n= 15; intravenous, n = 14). Median CD4 count was 130 cells/mm3 (IQR 66 - 253). Rifampicin geometric mean AUC0-24 was 42.9 $\mu$g{\textperiodcentered}h/mL (95{\%} CI, 24.5 – 75.0) for standard dose; 295.2 $\mu$g{\textperiodcentered}h/mL (95{\%} CI, 189.9 – 458.8) for high dose oral; and 206.5 $\mu$g{\textperiodcentered}h/mL (95{\%} CI, 154.6 – 275.8) for intravenous administration. Rifampicin AUC0-24 GMR was 1.44 (90{\%} CI, 0.84 - 2.21) and Cmax GMR was 0.89 (90{\%} CI, 0.63 – 1.23) for high dose oral with respect to intravenous dosing. Conclusions Plasma rifampicin AUC0-24 was higher after an oral 35 mg/kg dose compared with intravenous administration at 20 mg/kg dose over the first few days of TB treatment. Findings support oral rifampicin dosing in future tuberculous meningitis trials.},
author = {Wasserman, Sean and Davis, Angharad G and Stek, Cari and Chirehwa, Maxwell and Botha, Stephani and Daroowala, Remy and Bremer, Marise and Maxebengula, Mpumi and Koekemoer, Sonya and Goliath, Rene and Jackson, Amanda and Crede, Thomas and Naude, Jonathan and Szymanski, Patryk and Vallie, Yakoob and Moosa, Muhammed S and Wiesner, Lubbe and Black, John and Meintjes, Graeme and Maartens, Gary and Wilkinson, Robert J},
doi = {10.1128/AAC.00140-21},
file = {:C$\backslash$:/Users/01462563/AppData/Local/Mendeley Ltd./Mendeley Desktop/Downloaded/Wasserman et al. - 2021 - Plasma pharmacokinetics of high dose oral versus intravenous rifampicin in patients with tuberculous mening(2).pdf:pdf},
issn = {0066-4804},
journal = {Antimicrobial Agents and Chemotherapy},
keywords = {OA,fund{\_}ack,original},
mendeley-tags = {OA,fund{\_}ack,original},
month = {may},
number = {8},
pages = {e00140},
pmid = {33972248},
publisher = {American Society for Microbiology Journals},
title = {{Plasma pharmacokinetics of high dose oral versus intravenous rifampicin in patients with tuberculous meningitis: a randomized controlled trial}},
url = {http://aac.asm.org/lookup/doi/10.1128/AAC.00140-21},
volume = {65},
year = {2021}
}
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Materials and methods We performed a randomized parallel group pharmacokinetic study nested within a clinical trial of intensified antimicrobial therapy for tuberculous meningitis. HIV-positive participants with tuberculous meningitis were recruited from South African hospitals and randomized to one of three rifampicin dosing groups: standard (oral 10 mg/kg), high dose (oral 35 mg/kg), and intravenous (intravenous 20 mg/kg). Intensive pharmacokinetic sampling was done on day 3. Data were described using non-compartmental analysis and exposures compared by geometric mean ratio (GMR). Results Forty-six participants underwent pharmacokinetic sampling (standard dose, n = 17; high dose oral, n= 15; intravenous, n = 14). Median CD4 count was 130 cells/mm3 (IQR 66 - 253). Rifampicin geometric mean AUC0-24 was 42.9 $μ$g˙h/mL (95% CI, 24.5 – 75.0) for standard dose; 295.2 $μ$g˙h/mL (95% CI, 189.9 – 458.8) for high dose oral; and 206.5 $μ$g˙h/mL (95% CI, 154.6 – 275.8) for intravenous administration. Rifampicin AUC0-24 GMR was 1.44 (90% CI, 0.84 - 2.21) and Cmax GMR was 0.89 (90% CI, 0.63 – 1.23) for high dose oral with respect to intravenous dosing. Conclusions Plasma rifampicin AUC0-24 was higher after an oral 35 mg/kg dose compared with intravenous administration at 20 mg/kg dose over the first few days of TB treatment. Findings support oral rifampicin dosing in future tuberculous meningitis trials.","author":[{"propositions":[],"lastnames":["Wasserman"],"firstnames":["Sean"],"suffixes":[]},{"propositions":[],"lastnames":["Davis"],"firstnames":["Angharad","G"],"suffixes":[]},{"propositions":[],"lastnames":["Stek"],"firstnames":["Cari"],"suffixes":[]},{"propositions":[],"lastnames":["Chirehwa"],"firstnames":["Maxwell"],"suffixes":[]},{"propositions":[],"lastnames":["Botha"],"firstnames":["Stephani"],"suffixes":[]},{"propositions":[],"lastnames":["Daroowala"],"firstnames":["Remy"],"suffixes":[]},{"propositions":[],"lastnames":["Bremer"],"firstnames":["Marise"],"suffixes":[]},{"propositions":[],"lastnames":["Maxebengula"],"firstnames":["Mpumi"],"suffixes":[]},{"propositions":[],"lastnames":["Koekemoer"],"firstnames":["Sonya"],"suffixes":[]},{"propositions":[],"lastnames":["Goliath"],"firstnames":["Rene"],"suffixes":[]},{"propositions":[],"lastnames":["Jackson"],"firstnames":["Amanda"],"suffixes":[]},{"propositions":[],"lastnames":["Crede"],"firstnames":["Thomas"],"suffixes":[]},{"propositions":[],"lastnames":["Naude"],"firstnames":["Jonathan"],"suffixes":[]},{"propositions":[],"lastnames":["Szymanski"],"firstnames":["Patryk"],"suffixes":[]},{"propositions":[],"lastnames":["Vallie"],"firstnames":["Yakoob"],"suffixes":[]},{"propositions":[],"lastnames":["Moosa"],"firstnames":["Muhammed","S"],"suffixes":[]},{"propositions":[],"lastnames":["Wiesner"],"firstnames":["Lubbe"],"suffixes":[]},{"propositions":[],"lastnames":["Black"],"firstnames":["John"],"suffixes":[]},{"propositions":[],"lastnames":["Meintjes"],"firstnames":["Graeme"],"suffixes":[]},{"propositions":[],"lastnames":["Maartens"],"firstnames":["Gary"],"suffixes":[]},{"propositions":[],"lastnames":["Wilkinson"],"firstnames":["Robert","J"],"suffixes":[]}],"doi":"10.1128/AAC.00140-21","file":":C$\\$:/Users/01462563/AppData/Local/Mendeley Ltd./Mendeley Desktop/Downloaded/Wasserman et al. - 2021 - Plasma pharmacokinetics of high dose oral versus intravenous rifampicin in patients with tuberculous mening(2).pdf:pdf","issn":"0066-4804","journal":"Antimicrobial Agents and Chemotherapy","keywords":"OA,fund_ack,original","mendeley-tags":"OA,fund_ack,original","month":"may","number":"8","pages":"e00140","pmid":"33972248","publisher":"American Society for Microbiology Journals","title":"Plasma pharmacokinetics of high dose oral versus intravenous rifampicin in patients with tuberculous meningitis: a randomized controlled trial","url":"http://aac.asm.org/lookup/doi/10.1128/AAC.00140-21","volume":"65","year":"2021","bibtex":"@article{Wasserman2021a,\r\nabstract = {Background Higher doses of intravenous rifampicin may improve outcomes in tuberculous meningitis but is impractical in high burden settings. We hypothesized that plasma rifampicin exposures would be similar between oral 35 mg/kg and intravenous 20 mg/kg, which has been proposed for efficacy trials in tuberculous meningitis. Materials and methods We performed a randomized parallel group pharmacokinetic study nested within a clinical trial of intensified antimicrobial therapy for tuberculous meningitis. HIV-positive participants with tuberculous meningitis were recruited from South African hospitals and randomized to one of three rifampicin dosing groups: standard (oral 10 mg/kg), high dose (oral 35 mg/kg), and intravenous (intravenous 20 mg/kg). Intensive pharmacokinetic sampling was done on day 3. Data were described using non-compartmental analysis and exposures compared by geometric mean ratio (GMR). Results Forty-six participants underwent pharmacokinetic sampling (standard dose, n = 17; high dose oral, n= 15; intravenous, n = 14). Median CD4 count was 130 cells/mm3 (IQR 66 - 253). Rifampicin geometric mean AUC0-24 was 42.9 $\\mu$g{\\textperiodcentered}h/mL (95{\\%} CI, 24.5 – 75.0) for standard dose; 295.2 $\\mu$g{\\textperiodcentered}h/mL (95{\\%} CI, 189.9 – 458.8) for high dose oral; and 206.5 $\\mu$g{\\textperiodcentered}h/mL (95{\\%} CI, 154.6 – 275.8) for intravenous administration. Rifampicin AUC0-24 GMR was 1.44 (90{\\%} CI, 0.84 - 2.21) and Cmax GMR was 0.89 (90{\\%} CI, 0.63 – 1.23) for high dose oral with respect to intravenous dosing. Conclusions Plasma rifampicin AUC0-24 was higher after an oral 35 mg/kg dose compared with intravenous administration at 20 mg/kg dose over the first few days of TB treatment. Findings support oral rifampicin dosing in future tuberculous meningitis trials.},\r\nauthor = {Wasserman, Sean and Davis, Angharad G and Stek, Cari and Chirehwa, Maxwell and Botha, Stephani and Daroowala, Remy and Bremer, Marise and Maxebengula, Mpumi and Koekemoer, Sonya and Goliath, Rene and Jackson, Amanda and Crede, Thomas and Naude, Jonathan and Szymanski, Patryk and Vallie, Yakoob and Moosa, Muhammed S and Wiesner, Lubbe and Black, John and Meintjes, Graeme and Maartens, Gary and Wilkinson, Robert J},\r\ndoi = {10.1128/AAC.00140-21},\r\nfile = {:C$\\backslash$:/Users/01462563/AppData/Local/Mendeley Ltd./Mendeley Desktop/Downloaded/Wasserman et al. - 2021 - Plasma pharmacokinetics of high dose oral versus intravenous rifampicin in patients with tuberculous mening(2).pdf:pdf},\r\nissn = {0066-4804},\r\njournal = {Antimicrobial Agents and Chemotherapy},\r\nkeywords = {OA,fund{\\_}ack,original},\r\nmendeley-tags = {OA,fund{\\_}ack,original},\r\nmonth = {may},\r\nnumber = {8},\r\npages = {e00140},\r\npmid = {33972248},\r\npublisher = {American Society for Microbiology Journals},\r\ntitle = {{Plasma pharmacokinetics of high dose oral versus intravenous rifampicin in patients with tuberculous meningitis: a randomized controlled trial}},\r\nurl = {http://aac.asm.org/lookup/doi/10.1128/AAC.00140-21},\r\nvolume = {65},\r\nyear = {2021}\r\n}\r\n","author_short":["Wasserman, S.","Davis, A. 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