@article{Abdelgawad2022,
abstract = {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 {\&}reg; 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 underexposed compared to their outpatient counterparts.},
author = {Abdelgawad, Noha and Chirehwa, Maxwell and Schutz, Charlotte and Barr, David and Ward, Amy and Janssen, Saskia and Burton, Rosie and Wilkinson, Robert J. and Shey, Muki and Wiesner, Lubbe and McIlleron, Helen and Maartens, Gary and Meintjes, Graeme and Denti, Paolo},
doi = {10.12688/wellcomeopenres.17660.1},
file = {:C$\backslash$:/Users/01462563/AppData/Local/Mendeley Ltd./Mendeley Desktop/Downloaded/Abdelgawad et al. - 2022 - A comparison of the population pharmacokinetics of rifampicin, isoniazid and pyrazinamide between hospitalize.pdf:pdf},
isbn = {10.35802/211360},
issn = {2398-502X},
journal = {Wellcome Open Research},
keywords = {Data Curation,Hospitalization,Janssen S: Data Curation,Maartens G: Conceptualization,McIlleron H: Conceptualization,Meintjes G: Conceptualization,Modelling {\&} Simulation,OA,Population pharmacokinetics,Resources,Schutz C: Investigation,Shey M: Methodology,TB/HIV,Tuberculosis,Ward A: Investigation,Wiesner L: Methodology,Wilkinson RJ: Conceptualization,Writing-Review {\&} Editing,fund{\_}ack,original},
mendeley-tags = {OA,fund{\_}ack,original},
month = {feb},
pages = {72},
publisher = {F1000 Research Limited},
title = {{A comparison of the population pharmacokinetics of rifampicin, isoniazid and pyrazinamide between hospitalized and non-hospitalized tuberculosis patients with or without HIV [version 1; peer review: awaiting peer review]}},
url = {https://wellcomeopenresearch.org/articles/7-72},
volume = {7},
year = {2022}
}

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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 underexposed compared to their outpatient counterparts.","author":[{"propositions":[],"lastnames":["Abdelgawad"],"firstnames":["Noha"],"suffixes":[]},{"propositions":[],"lastnames":["Chirehwa"],"firstnames":["Maxwell"],"suffixes":[]},{"propositions":[],"lastnames":["Schutz"],"firstnames":["Charlotte"],"suffixes":[]},{"propositions":[],"lastnames":["Barr"],"firstnames":["David"],"suffixes":[]},{"propositions":[],"lastnames":["Ward"],"firstnames":["Amy"],"suffixes":[]},{"propositions":[],"lastnames":["Janssen"],"firstnames":["Saskia"],"suffixes":[]},{"propositions":[],"lastnames":["Burton"],"firstnames":["Rosie"],"suffixes":[]},{"propositions":[],"lastnames":["Wilkinson"],"firstnames":["Robert","J."],"suffixes":[]},{"propositions":[],"lastnames":["Shey"],"firstnames":["Muki"],"suffixes":[]},{"propositions":[],"lastnames":["Wiesner"],"firstnames":["Lubbe"],"suffixes":[]},{"propositions":[],"lastnames":["McIlleron"],"firstnames":["Helen"],"suffixes":[]},{"propositions":[],"lastnames":["Maartens"],"firstnames":["Gary"],"suffixes":[]},{"propositions":[],"lastnames":["Meintjes"],"firstnames":["Graeme"],"suffixes":[]},{"propositions":[],"lastnames":["Denti"],"firstnames":["Paolo"],"suffixes":[]}],"doi":"10.12688/wellcomeopenres.17660.1","file":":C$\\$:/Users/01462563/AppData/Local/Mendeley Ltd./Mendeley Desktop/Downloaded/Abdelgawad et al. - 2022 - A comparison of the population pharmacokinetics of rifampicin, isoniazid and pyrazinamide between hospitalize.pdf:pdf","isbn":"10.35802/211360","issn":"2398-502X","journal":"Wellcome Open Research","keywords":"Data Curation,Hospitalization,Janssen S: Data Curation,Maartens G: Conceptualization,McIlleron H: Conceptualization,Meintjes G: Conceptualization,Modelling & Simulation,OA,Population pharmacokinetics,Resources,Schutz C: Investigation,Shey M: Methodology,TB/HIV,Tuberculosis,Ward A: Investigation,Wiesner L: Methodology,Wilkinson RJ: Conceptualization,Writing-Review & Editing,fund_ack,original","mendeley-tags":"OA,fund_ack,original","month":"feb","pages":"72","publisher":"F1000 Research Limited","title":"A comparison of the population pharmacokinetics of rifampicin, isoniazid and pyrazinamide between hospitalized and non-hospitalized tuberculosis patients with or without HIV [version 1; peer review: awaiting peer review]","url":"https://wellcomeopenresearch.org/articles/7-72","volume":"7","year":"2022","bibtex":"@article{Abdelgawad2022,\r\nabstract = {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 {\\&}reg; 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 underexposed compared to their outpatient counterparts.},\r\nauthor = {Abdelgawad, Noha and Chirehwa, Maxwell and Schutz, Charlotte and Barr, David and Ward, Amy and Janssen, Saskia and Burton, Rosie and Wilkinson, Robert J. and Shey, Muki and Wiesner, Lubbe and McIlleron, Helen and Maartens, Gary and Meintjes, Graeme and Denti, Paolo},\r\ndoi = {10.12688/wellcomeopenres.17660.1},\r\nfile = {:C$\\backslash$:/Users/01462563/AppData/Local/Mendeley Ltd./Mendeley Desktop/Downloaded/Abdelgawad et al. - 2022 - A comparison of the population pharmacokinetics of rifampicin, isoniazid and pyrazinamide between hospitalize.pdf:pdf},\r\nisbn = {10.35802/211360},\r\nissn = {2398-502X},\r\njournal = {Wellcome Open Research},\r\nkeywords = {Data Curation,Hospitalization,Janssen S: Data Curation,Maartens G: Conceptualization,McIlleron H: Conceptualization,Meintjes G: Conceptualization,Modelling {\\&} Simulation,OA,Population pharmacokinetics,Resources,Schutz C: Investigation,Shey M: Methodology,TB/HIV,Tuberculosis,Ward A: Investigation,Wiesner L: Methodology,Wilkinson RJ: Conceptualization,Writing-Review {\\&} Editing,fund{\\_}ack,original},\r\nmendeley-tags = {OA,fund{\\_}ack,original},\r\nmonth = {feb},\r\npages = {72},\r\npublisher = {F1000 Research Limited},\r\ntitle = {{A comparison of the population pharmacokinetics of rifampicin, isoniazid and pyrazinamide between hospitalized and non-hospitalized tuberculosis patients with or without HIV [version 1; peer review: awaiting peer review]}},\r\nurl = {https://wellcomeopenresearch.org/articles/7-72},\r\nvolume = {7},\r\nyear = {2022}\r\n}\r\n","author_short":["Abdelgawad, N.","Chirehwa, M.","Schutz, C.","Barr, D.","Ward, A.","Janssen, S.","Burton, R.","Wilkinson, R. 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