@article{Chabala2021,
abstract = {Background Dispersible pediatric fixed-dose combination (FDC) tablets delivering higher doses of first-line antituberculosis drugs in World Health Organization–recommended weight bands were introduced in 2015. We report the first pharmacokinetic data for these FDC tablets in Zambian and South African children in the treatment-shortening SHINE trial. Methods Children weighing 4.0–7.9, 8.0–11.9, 12.0–15.9, or 16.0–24.9 kg received 1, 2, 3, or 4 tablets daily, respectively (rifampicin/isoniazid/pyrazinamide [75/50/150 mg], with or without 100 mg ethambutol, or rifampicin/isoniazid [75/50 mg]). Children 25.0–36.9 kg received doses recommended for adults {\textless}37 kg (300, 150, 800, and 550 mg/d, respectively, for rifampicin, isoniazid, pyrazinamide, and ethambutol). Pharmacokinetics were evaluated after at least 2 weeks of treatment. Results In the 77 children evaluated, the median age (interquartile range) was 3.7 (1.4–6.6) years; 40 (52{\%}) were male and 20 (26{\%}) were human immunodeficiency virus positive. The median area under the concentration-time curve from 0 to 24 hours for rifampicin, isoniazid, pyrazinamide, and ethambutol was 32.5 (interquartile range, 20.1–45.1), 16.7 (9.2–25.9), 317 (263–399), and 9.5 (7.5–11.5) mg⋅h/L, respectively, and lower in children than in adults for rifampicin in the 4.0–7.9-, 8–11.9-, and ≥25-kg weight bands, isoniazid in the 4.0–7.9-kg and ≥25-kg weight bands, and ethambutol in all 5 weight bands. Pyrazinamide exposures were similar to those in adults. Conclusions Recommended weight band–based FDC doses result in lower drug exposures in children in lower weight bands and in those ≥25 kg (receiving adult doses). Further adjustments to current doses are needed to match current target exposures in adults. The use of ethambutol at the current World Health Organization–recommended doses requires further evaluation.},
author = {Chabala, Chishala and trial Team, on Behalf of the SHINE and Turkova, Anna and trial Team, on Behalf of the SHINE and Hesseling, Anneke C and trial Team, on Behalf of the SHINE and Zimba, Kevin M and trial Team, on Behalf of the SHINE and van der Zalm, Marieke and trial Team, on Behalf of the SHINE and Kapasa, Monica and trial Team, on Behalf of the SHINE and Palmer, Megan and trial Team, on Behalf of the SHINE and Chirehwa, Maxwell and trial Team, on Behalf of the SHINE and Wiesner, Lubbe and trial Team, on Behalf of the SHINE and Wobudeya, Eric and trial Team, on Behalf of the SHINE and Kinikar, Aarti and trial Team, on Behalf of the SHINE and Mave, Vidya and trial Team, on Behalf of the SHINE and Hissar, Syed and trial Team, on Behalf of the SHINE and Choo, Louise and trial Team, on Behalf of the SHINE and LeBeau, Kristen and trial Team, on Behalf of the SHINE and Mulenga, Veronica and trial Team, on Behalf of the SHINE and Aarnoutse, Robb and trial Team, on Behalf of the SHINE and Gibb, Diana and trial Team, on Behalf of the SHINE and McIlleron, Helen and trial Team, on Behalf of the SHINE},
doi = {10.1093/CID/CIAB725},
file = {:C$\backslash$:/Users/01462563/AppData/Local/Mendeley Ltd./Mendeley Desktop/Downloaded/Chabala et al. - 2022 - Pharmacokinetics of first-line drugs in children with tuberculosis using WHO-recommended weight band doses and f.pdf:pdf},
journal = {Clinical Infectious Diseases},
keywords = {OA,adult,child,ethambutol,fund{\_}not{\_}ack,original,pyrazinamide,world health organization},
mendeley-tags = {OA,fund{\_}not{\_}ack,original},
month = {aug},
number = {10},
pages = {1767--1775},
pmid = {34420049},
title = {{Pharmacokinetics of first-line drugs in children with tuberculosis using WHO-recommended weight band doses and formulations}},
url = {https://academic.oup.com/cid/advance-article/doi/10.1093/cid/ciab725/6356214},
volume = {74},
year = {2022}
}

{"_id":"EvksBWhGgF8MNNdbN","bibbaseid":"chabala-trialteam-turkova-trialteam-hesseling-trialteam-zimba-trialteam-etal-pharmacokineticsoffirstlinedrugsinchildrenwithtuberculosisusingwhorecommendedweightbanddosesandformulations-2022","author_short":["Chabala, C.","trial Team, o. B. o. t. S.","Turkova, A.","trial Team, o. B. o. t. S.","Hesseling, A. C","trial Team, o. B. o. t. S.","Zimba, K. M","trial Team, o. B. o. t. S.","van der Zalm, M.","trial Team, o. B. o. t. S.","Kapasa, M.","trial Team, o. B. o. t. S.","Palmer, M.","trial Team, o. B. o. t. S.","Chirehwa, M.","trial Team, o. B. o. t. S.","Wiesner, L.","trial Team, o. B. o. t. S.","Wobudeya, E.","trial Team, o. B. o. t. S.","Kinikar, A.","trial Team, o. B. o. t. S.","Mave, V.","trial Team, o. B. o. t. S.","Hissar, S.","trial Team, o. B. o. t. S.","Choo, L.","trial Team, o. B. o. t. S.","LeBeau, K.","trial Team, o. B. o. t. S.","Mulenga, V.","trial Team, o. B. o. t. S.","Aarnoutse, R.","trial Team, o. B. o. t. S.","Gibb, D.","trial Team, o. B. o. t. S.","McIlleron, H.","trial Team, o. B. o. t. S."],"bibdata":{"bibtype":"article","type":"article","abstract":"Background Dispersible pediatric fixed-dose combination (FDC) tablets delivering higher doses of first-line antituberculosis drugs in World Health Organization–recommended weight bands were introduced in 2015. We report the first pharmacokinetic data for these FDC tablets in Zambian and South African children in the treatment-shortening SHINE trial. Methods Children weighing 4.0–7.9, 8.0–11.9, 12.0–15.9, or 16.0–24.9 kg received 1, 2, 3, or 4 tablets daily, respectively (rifampicin/isoniazid/pyrazinamide [75/50/150 mg], with or without 100 mg ethambutol, or rifampicin/isoniazid [75/50 mg]). Children 25.0–36.9 kg received doses recommended for adults \\textless37 kg (300, 150, 800, and 550 mg/d, respectively, for rifampicin, isoniazid, pyrazinamide, and ethambutol). Pharmacokinetics were evaluated after at least 2 weeks of treatment. Results In the 77 children evaluated, the median age (interquartile range) was 3.7 (1.4–6.6) years; 40 (52%) were male and 20 (26%) were human immunodeficiency virus positive. The median area under the concentration-time curve from 0 to 24 hours for rifampicin, isoniazid, pyrazinamide, and ethambutol was 32.5 (interquartile range, 20.1–45.1), 16.7 (9.2–25.9), 317 (263–399), and 9.5 (7.5–11.5) mg⋅h/L, respectively, and lower in children than in adults for rifampicin in the 4.0–7.9-, 8–11.9-, and ≥25-kg weight bands, isoniazid in the 4.0–7.9-kg and ≥25-kg weight bands, and ethambutol in all 5 weight bands. Pyrazinamide exposures were similar to those in adults. Conclusions Recommended weight band–based FDC doses result in lower drug exposures in children in lower weight bands and in those ≥25 kg (receiving adult doses). Further adjustments to current doses are needed to match current target exposures in adults. The use of ethambutol at the current World Health Organization–recommended doses requires further evaluation.","author":[{"propositions":[],"lastnames":["Chabala"],"firstnames":["Chishala"],"suffixes":[]},{"propositions":["trial"],"lastnames":["Team"],"firstnames":["on","Behalf","of","the","SHINE"],"suffixes":[]},{"propositions":[],"lastnames":["Turkova"],"firstnames":["Anna"],"suffixes":[]},{"propositions":["trial"],"lastnames":["Team"],"firstnames":["on","Behalf","of","the","SHINE"],"suffixes":[]},{"propositions":[],"lastnames":["Hesseling"],"firstnames":["Anneke","C"],"suffixes":[]},{"propositions":["trial"],"lastnames":["Team"],"firstnames":["on","Behalf","of","the","SHINE"],"suffixes":[]},{"propositions":[],"lastnames":["Zimba"],"firstnames":["Kevin","M"],"suffixes":[]},{"propositions":["trial"],"lastnames":["Team"],"firstnames":["on","Behalf","of","the","SHINE"],"suffixes":[]},{"propositions":["van","der"],"lastnames":["Zalm"],"firstnames":["Marieke"],"suffixes":[]},{"propositions":["trial"],"lastnames":["Team"],"firstnames":["on","Behalf","of","the","SHINE"],"suffixes":[]},{"propositions":[],"lastnames":["Kapasa"],"firstnames":["Monica"],"suffixes":[]},{"propositions":["trial"],"lastnames":["Team"],"firstnames":["on","Behalf","of","the","SHINE"],"suffixes":[]},{"propositions":[],"lastnames":["Palmer"],"firstnames":["Megan"],"suffixes":[]},{"propositions":["trial"],"lastnames":["Team"],"firstnames":["on","Behalf","of","the","SHINE"],"suffixes":[]},{"propositions":[],"lastnames":["Chirehwa"],"firstnames":["Maxwell"],"suffixes":[]},{"propositions":["trial"],"lastnames":["Team"],"firstnames":["on","Behalf","of","the","SHINE"],"suffixes":[]},{"propositions":[],"lastnames":["Wiesner"],"firstnames":["Lubbe"],"suffixes":[]},{"propositions":["trial"],"lastnames":["Team"],"firstnames":["on","Behalf","of","the","SHINE"],"suffixes":[]},{"propositions":[],"lastnames":["Wobudeya"],"firstnames":["Eric"],"suffixes":[]},{"propositions":["trial"],"lastnames":["Team"],"firstnames":["on","Behalf","of","the","SHINE"],"suffixes":[]},{"propositions":[],"lastnames":["Kinikar"],"firstnames":["Aarti"],"suffixes":[]},{"propositions":["trial"],"lastnames":["Team"],"firstnames":["on","Behalf","of","the","SHINE"],"suffixes":[]},{"propositions":[],"lastnames":["Mave"],"firstnames":["Vidya"],"suffixes":[]},{"propositions":["trial"],"lastnames":["Team"],"firstnames":["on","Behalf","of","the","SHINE"],"suffixes":[]},{"propositions":[],"lastnames":["Hissar"],"firstnames":["Syed"],"suffixes":[]},{"propositions":["trial"],"lastnames":["Team"],"firstnames":["on","Behalf","of","the","SHINE"],"suffixes":[]},{"propositions":[],"lastnames":["Choo"],"firstnames":["Louise"],"suffixes":[]},{"propositions":["trial"],"lastnames":["Team"],"firstnames":["on","Behalf","of","the","SHINE"],"suffixes":[]},{"propositions":[],"lastnames":["LeBeau"],"firstnames":["Kristen"],"suffixes":[]},{"propositions":["trial"],"lastnames":["Team"],"firstnames":["on","Behalf","of","the","SHINE"],"suffixes":[]},{"propositions":[],"lastnames":["Mulenga"],"firstnames":["Veronica"],"suffixes":[]},{"propositions":["trial"],"lastnames":["Team"],"firstnames":["on","Behalf","of","the","SHINE"],"suffixes":[]},{"propositions":[],"lastnames":["Aarnoutse"],"firstnames":["Robb"],"suffixes":[]},{"propositions":["trial"],"lastnames":["Team"],"firstnames":["on","Behalf","of","the","SHINE"],"suffixes":[]},{"propositions":[],"lastnames":["Gibb"],"firstnames":["Diana"],"suffixes":[]},{"propositions":["trial"],"lastnames":["Team"],"firstnames":["on","Behalf","of","the","SHINE"],"suffixes":[]},{"propositions":[],"lastnames":["McIlleron"],"firstnames":["Helen"],"suffixes":[]},{"propositions":["trial"],"lastnames":["Team"],"firstnames":["on","Behalf","of","the","SHINE"],"suffixes":[]}],"doi":"10.1093/CID/CIAB725","file":":C$\\$:/Users/01462563/AppData/Local/Mendeley Ltd./Mendeley Desktop/Downloaded/Chabala et al. - 2022 - Pharmacokinetics of first-line drugs in children with tuberculosis using WHO-recommended weight band doses and f.pdf:pdf","journal":"Clinical Infectious Diseases","keywords":"OA,adult,child,ethambutol,fund_not_ack,original,pyrazinamide,world health organization","mendeley-tags":"OA,fund_not_ack,original","month":"aug","number":"10","pages":"1767–1775","pmid":"34420049","title":"Pharmacokinetics of first-line drugs in children with tuberculosis using WHO-recommended weight band doses and formulations","url":"https://academic.oup.com/cid/advance-article/doi/10.1093/cid/ciab725/6356214","volume":"74","year":"2022","bibtex":"@article{Chabala2021,\r\nabstract = {Background Dispersible pediatric fixed-dose combination (FDC) tablets delivering higher doses of first-line antituberculosis drugs in World Health Organization–recommended weight bands were introduced in 2015. We report the first pharmacokinetic data for these FDC tablets in Zambian and South African children in the treatment-shortening SHINE trial. Methods Children weighing 4.0–7.9, 8.0–11.9, 12.0–15.9, or 16.0–24.9 kg received 1, 2, 3, or 4 tablets daily, respectively (rifampicin/isoniazid/pyrazinamide [75/50/150 mg], with or without 100 mg ethambutol, or rifampicin/isoniazid [75/50 mg]). Children 25.0–36.9 kg received doses recommended for adults {\\textless}37 kg (300, 150, 800, and 550 mg/d, respectively, for rifampicin, isoniazid, pyrazinamide, and ethambutol). Pharmacokinetics were evaluated after at least 2 weeks of treatment. Results In the 77 children evaluated, the median age (interquartile range) was 3.7 (1.4–6.6) years; 40 (52{\\%}) were male and 20 (26{\\%}) were human immunodeficiency virus positive. The median area under the concentration-time curve from 0 to 24 hours for rifampicin, isoniazid, pyrazinamide, and ethambutol was 32.5 (interquartile range, 20.1–45.1), 16.7 (9.2–25.9), 317 (263–399), and 9.5 (7.5–11.5) mg⋅h/L, respectively, and lower in children than in adults for rifampicin in the 4.0–7.9-, 8–11.9-, and ≥25-kg weight bands, isoniazid in the 4.0–7.9-kg and ≥25-kg weight bands, and ethambutol in all 5 weight bands. Pyrazinamide exposures were similar to those in adults. Conclusions Recommended weight band–based FDC doses result in lower drug exposures in children in lower weight bands and in those ≥25 kg (receiving adult doses). Further adjustments to current doses are needed to match current target exposures in adults. The use of ethambutol at the current World Health Organization–recommended doses requires further evaluation.},\r\nauthor = {Chabala, Chishala and trial Team, on Behalf of the SHINE and Turkova, Anna and trial Team, on Behalf of the SHINE and Hesseling, Anneke C and trial Team, on Behalf of the SHINE and Zimba, Kevin M and trial Team, on Behalf of the SHINE and van der Zalm, Marieke and trial Team, on Behalf of the SHINE and Kapasa, Monica and trial Team, on Behalf of the SHINE and Palmer, Megan and trial Team, on Behalf of the SHINE and Chirehwa, Maxwell and trial Team, on Behalf of the SHINE and Wiesner, Lubbe and trial Team, on Behalf of the SHINE and Wobudeya, Eric and trial Team, on Behalf of the SHINE and Kinikar, Aarti and trial Team, on Behalf of the SHINE and Mave, Vidya and trial Team, on Behalf of the SHINE and Hissar, Syed and trial Team, on Behalf of the SHINE and Choo, Louise and trial Team, on Behalf of the SHINE and LeBeau, Kristen and trial Team, on Behalf of the SHINE and Mulenga, Veronica and trial Team, on Behalf of the SHINE and Aarnoutse, Robb and trial Team, on Behalf of the SHINE and Gibb, Diana and trial Team, on Behalf of the SHINE and McIlleron, Helen and trial Team, on Behalf of the SHINE},\r\ndoi = {10.1093/CID/CIAB725},\r\nfile = {:C$\\backslash$:/Users/01462563/AppData/Local/Mendeley Ltd./Mendeley Desktop/Downloaded/Chabala et al. - 2022 - Pharmacokinetics of first-line drugs in children with tuberculosis using WHO-recommended weight band doses and f.pdf:pdf},\r\njournal = {Clinical Infectious Diseases},\r\nkeywords = {OA,adult,child,ethambutol,fund{\\_}not{\\_}ack,original,pyrazinamide,world health organization},\r\nmendeley-tags = {OA,fund{\\_}not{\\_}ack,original},\r\nmonth = {aug},\r\nnumber = {10},\r\npages = {1767--1775},\r\npmid = {34420049},\r\ntitle = {{Pharmacokinetics of first-line drugs in children with tuberculosis using WHO-recommended weight band doses and formulations}},\r\nurl = {https://academic.oup.com/cid/advance-article/doi/10.1093/cid/ciab725/6356214},\r\nvolume = {74},\r\nyear = {2022}\r\n}\r\n","author_short":["Chabala, C.","trial Team, o. 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