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{Abdelgawad:2022:10.12688/wellcomeopenres.17660.1,
author = {Abdelgawad, N and Chirehwa, M and Schutz, C and Barr, D and Ward, A and Janssen, S and Burton, R and Wilkinson, R and Shey, M and Wiesner, L and McIlleron, H and Maartens, G and Meintjes, G and Denti, P},
doi = {10.12688/wellcomeopenres.17660.1},
journal = {Wellcome Open Research},
pages = {1--20},
title = {A comparison of the population pharmacokinetics of rifampicin, isoniazid and pyrazinamide between hospitalized and non-hospitalized tuberculosis patients with or without HIV},
url = {http://dx.doi.org/10.12688/wellcomeopenres.17660.1},
volume = {7},
year = {2022}
}
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RIS format (EndNote, RefMan)

TY  - JOUR
AB  - Background.Early mortality among hospitalized HIV-associated tuberculosis (TB/HIV) patients is high despite treatment. The pharmacokinetics of rifampicin, isoniazid, and pyrazinamide were investigated in hospitalized TB/HIV patients and a cohort of outpatients with TB (with or without HIV) to determine whether drug exposures differed between groups.Methods.Standard first-line TB treatment was given daily as per national guidelines, which consisted of oral 4-drug fixed-dose combination tablets containing 150 mg rifampicin, 75 mg isoniazid, 400 mg pyrazinamide, and 275 mg ethambutol. Plasma samples were drawn on the 3rd day of treatment over eight hours post-dose. Rifampicin, isoniazid, and pyrazinamide in plasma were quantified and NONMEM® was used to analyze the data.Results.Data from 60 hospitalized patients (11 of whom died within 12 weeks of starting treatment) and 48 outpatients were available. Median (range) weight and age were 56 (35 - 88) kg, and 37 (19 - 77) years, respectively. Bioavailability and clearance of the three drugs were similar between TB/HIV hospitalized and TB outpatients. However, rifampicin’s absorption was slower in hospitalized patients than in outpatients; mean absorption time was 49.9% and 154% more in hospitalized survivors and hospitalized deaths, respectively, than in outpatients. Higher levels of conjugated bilirubin correlated with lower rifampicin clearance. Isoniazid’s clearance estimates were 25.5 L/h for fast metabolizers and 9.76 L/h for slow metabolizers. Pyrazinamide’s clearance was more variable among hospitalized patients. The variability in clearance among patients  was 1.70 and 3.56 times more for hospitalized survivors and hospitalized deaths, respectively, than outpatients.  Conclusion.We showed that the pharmacokinetics of first-line TB drugs are not substantially different between hospitalized TB/HIV patients and TB (with or without HIV) outpatients. Hospitalized patients do not seem to be underex
AU  - Abdelgawad,N
AU  - Chirehwa,M
AU  - Schutz,C
AU  - Barr,D
AU  - Ward,A
AU  - Janssen,S
AU  - Burton,R
AU  - Wilkinson,R
AU  - Shey,M
AU  - Wiesner,L
AU  - McIlleron,H
AU  - Maartens,G
AU  - Meintjes,G
AU  - Denti,P
DO  - 10.12688/wellcomeopenres.17660.1
EP  - 20
PY  - 2022///
SN  - 2398-502X
SP  - 1
TI  - A comparison of the population pharmacokinetics of rifampicin, isoniazid and pyrazinamide between hospitalized and non-hospitalized tuberculosis patients with or without HIV
T2  - Wellcome Open Research
UR  - http://dx.doi.org/10.12688/wellcomeopenres.17660.1
UR  - https://wellcomeopenresearch.org/articles/7-72/v1
UR  - http://hdl.handle.net/10044/1/100647
VL  - 7
ER  -
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