Imperial College London
Professor Robert Wilkinson

ProfessorRobertWilkinson

Faculty of Medicine, Department of Infectious Disease

Professor in Infectious Diseases
 
 
 
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Contact

 

r.j.wilkinson Website

 
 
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Location

 

Commonwealth BuildingHammersmith Campus

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Summary

 

Publications

Citation

BibTex format

@article{Wasserman:2021:10.1128/AAC.00140-21,
author = {Wasserman, S and Davis, AG and Stek, C and Chirehwa, M and Botha, S and Daroowala, R and Bremer, M and Maxebengula, M and Koekemoer, S and Goliath, RT and Jackson, A and Crede, T and Naude, J and Szymanski, P and Vallie, Y and Moosa, MS and Wiesner, L and Black, J and Meintjes, G and Maartens, G and Wilkinson, RJ},
doi = {10.1128/AAC.00140-21},
journal = {Antimicrobial Agents and Chemotherapy},
pages = {1--12},
title = {Plasma pharmacokinetics of high dose oral versus intravenous rifampicin in patients with tuberculous meningitis: a randomized controlled trial},
url = {http://dx.doi.org/10.1128/AAC.00140-21},
volume = {65},
year = {2021}
}
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RIS format (EndNote, RefMan)

TY  - JOUR
AB  - BackgroundHigher 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 methodsWe 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).ResultsForty-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 μg·h/mL (95% CI, 24.5 – 75.0) for standard dose; 295.2 μg·h/mL (95% CI, 189.9 – 458.8) for high dose oral; and 206.5 μg·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.ConclusionsPlasma 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.
AU  - Wasserman,S
AU  - Davis,AG
AU  - Stek,C
AU  - Chirehwa,M
AU  - Botha,S
AU  - Daroowala,R
AU  - Bremer,M
AU  - Maxebengula,M
AU  - Koekemoer,S
AU  - Goliath,RT
AU  - Jackson,A
AU  - Crede,T
AU  - Naude,J
AU  - Szymanski,P
AU  - Vallie,Y
AU  - Moosa,MS
AU  - Wiesner,L
AU  - Black,J
AU  - Meintjes,G
AU  - Maartens,G
AU  - Wilkinson,RJ
DO  - 10.1128/AAC.00140-21
EP  - 12
PY  - 2021///
SN  - 0066-4804
SP  - 1
TI  - Plasma pharmacokinetics of high dose oral versus intravenous rifampicin in patients with tuberculous meningitis: a randomized controlled trial
T2  - Antimicrobial Agents and Chemotherapy
UR  - http://dx.doi.org/10.1128/AAC.00140-21
UR  - https://journals.asm.org/doi/10.1128/AAC.00140-21
UR  - http://hdl.handle.net/10044/1/89664
VL  - 65
ER  -
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