@article{Gafar2022,
abstract = {Background Suboptimal exposure to antituberculosis drugs has been associated with unfavourable treatment outcomes. We aimed to investigate estimates and determinants of first-line antituberculosis drug pharmacokinetics in children and adolescents at a global level. Methods We systematically searched MEDLINE, Embase, and Web of Science (1990–2021) for pharmacokinetic studies of first-line antituberculosis drugs in children and adolescents. Individual patient data were obtained from authors of eligible studies. Summary estimates of total/extrapolated area under the plasma concentration-time curve (AUC0–24) and peak plasma concentration (Cmax) were assessed with random-effects models, normalised with current WHO-recommended paediatric doses. Determinants of AUC0–24 and Cmax were assessed with linear mixed-effects models. Results Of 55 eligible studies, individual patient data were available for 39 (71{\%}), including 1628 participants from 12 countries. Geometric means (95{\%} CIs) of steady-state AUC0–24 were summarised for isoniazid (18.7 [15.5−22.6] h{\textperiodcentered}mg{\textperiodcentered}L−1), rifampicin (34.4 [29.4−40.3] h{\textperiodcentered}mg{\textperiodcentered}L−1), pyrazinamide (375.0 [339.9−413.7] h{\textperiodcentered}mg{\textperiodcentered}L−1), and ethambutol (8.0 [6.4−10.0] h{\textperiodcentered}mg{\textperiodcentered}L−1). Our multivariate models indicated that younger age (especially {\textless}2 years) and HIV-positive status were associated with lower AUC0–24 for all antituberculosis drugs, while severe malnutrition was associated with lower AUC0–24 for isoniazid and pyrazinamide. N-acetyltransferase 2 rapid acetylators had lower isoniazid AUC0–24 and slow acetylators had higher isoniazid AUC0–24 than intermediate acetylators. Determinants of Cmax were generally similar to those for AUC0–24. Conclusion This study provides the most comprehensive estimates of plasma exposures to first-line antituberculosis drugs in children and adolescents. Key determinants of drug exposures were identified. These may be relevant for population-specific dose adjustment or individualised therapeutic drug monitoring. Footnotes This manuscript has recently been accepted for publication in the European Respiratory Journal . It is published here in its accepted form prior to copyediting and typesetting by our production team. After these production processes are complete and the authors have approved the resulting proofs, the article will move to the latest issue of the ERJ online. Please open or download the PDF to view this article. Conflict of interest: HSS reports grants from the NIH/IMPAACT; and honoraria from Ann Lake publications − sponsored by Johnson {\&} Johnson − for an educational publication on the management of MDR-TB in children. Conflict of interest: AB reports grants from IMPAACT, UNITAID; lecture honoraria from Sandoz; support for attending PENTA PIM meeting; and received generic LPV/r, 3TC and ABC for the PETITE study. Conflict of interest: DJB reports support for attending a meeting from ViiV pharmaceuticals; and attendance fees for an Advisory board meeting from ViiV pharmaceuticals. Conflict of interest: LC reports grants from the UKRI MRC DfID Wellcome NIHR Joint Global Health Trials, TB Alliance Support for trial drug purchase, and UKRI COVID-19 Grant Extension Allocation Award. Conflict of interest: PD reports a grant for WHO expert review for TB drugs in children. Conflict of interest: SMG reports participation on a Data Safety Monitoring Board for the TB CHAMP trial; and leadership roles as a co-chair for Guidelines Development Committee of the WHO updated recommendations and consolidated guidelines on child and adolescents TB, and as a core member for the WHO Child and Adolescent TB Working Group. Conflict of interest: SKH reports grants from the NIH, DANIDA, and EDTCP; royalties or licenses from UpToDate; and honoraria for lectures from Henry Stewart Talks. Conflict of interest: AK reports a grant from the NIH/NICHD. Conflict of interest: VM reports grants from the NIH and CDC. Conflict of interest: CAP reports a grant from the NIH. Conflict of interest: VR reports a grant from the Delhi State TB Association; and leadership roles as a member of the Delhi State TB Association and the MAMC TB Committee. Conflict of interest: EMS reports grants from the NWO personal Veni, IMI UNITE4TB consortium, TB Alliance, UNITAID BenefitKids consortium, WHO expert review, NIH support for IMPAACT studies, Blueprint, Probex, ACTG study Clo-FAST, Janssen pharmaceuticals, EDCTP suport PanTB-HM, and Legochem; and leadership of fiduciary roles in ISOP DI{\&}E committee and BenNeLux PMX organizing committee. Conflict of interest: UT reports participation on a Data Safety Monitoring Board for an ICMR TB trial. Conflict of interest: TAT reports grants from the NIH and the University of Virginia. Conflict of interest: DJT reports a grant from Chiesi; consulting fees from Pure IMS and Sanguin; and participation on a Data Safety Monitoring Board for the FORMAT trial. Conflict of interest: AT reports grants from the UKRI MRC DfID Wellcome NIHR Joint Global Health Trials and the MRC Grants for core funding of the Medical Research Council Clinical Trials Unit at the UCL; and TB Alliance Support for SHINE trial drug purchase. Conflict of interest: All of this work was declared by the authors to be outside the submitted work. Conflict of interest: All other authors declare no competing interests.},
author = {Gafar, Fajri and Wasmann, Roeland E and McIlleron, Helen M and Aarnoutse, Rob E and Schaaf, H Simon and Marais, Ben J and Agarwal, Dipti and Antwi, Sampson and Bang, Nguyen D and Bekker, Adrie and Bell, David J and Chabala, Chishala and Choo, Louise and Davies, Geraint R and Day, Jeremy N and Dayal, Rajeshwar and Denti, Paolo and Donald, Peter R and Engidawork, Ephrem and Garcia-Prats, Anthony J and Gibb, Diana and Graham, Stephen M and Hesseling, Anneke C and Heysell, Scott K and Idris, Misgana I and Kabra, Sushil K and Kinikar, Aarti and Kumar, Agibothu K Hemanth and Kwara, Awewura and Lodha, Rakesh and Magis-Escurra, Cecile and Martinez, Nilza and Mathew, Binu S and Mave, Vidya and Mduma, Estomih and Mlotha-Mitole, Rachel and Mpagama, Stellah G and Mukherjee, Aparna and Nataprawira, Heda M and Peloquin, Charles A and Pouplin, Thomas and Ramachandran, Geetha and Ranjalkar, Jaya and Roy, Vandana and Ruslami, Rovina and Shah, Ira and Singh, Yatish and Sturkenboom, Marieke G G and Svensson, Elin M and Swaminathan, Soumya and Thatte, Urmila and Thee, Stephanie and Thomas, Tania A and Tikiso, Tjokosela and Touw, Daan J and Turkova, Anna and Velpandian, Thirumurthy and Verhagen, Lilly M and Winckler, Jana L and Yang, Hongmei and Yunivita, Vycke and Taxis, Katja and Stevens, Jasper and Alffenaar, Jan-Willem C and Drugs, for the Global Collaborative Group for Meta-Analysis of Paediatric Individual Patient Data in Pharmacokinetics of Anti-TB},
doi = {10.1183/13993003.01596-2022},
issn = {0903-1936},
journal = {European Respiratory Journal},
keywords = {OA,OA{\_}PMC,fund{\_}not{\_}ack,review},
mendeley-tags = {OA,OA{\_}PMC,fund{\_}not{\_}ack,review},
month = {nov},
number = {3},
pages = {2201596},
pmid = {36328357},
publisher = {European Respiratory Society},
title = {{Global estimates and determinants of antituberculosis drug pharmacokinetics in children and adolescents: a systematic review and individual patient data meta-analysis}},
url = {https://erj.ersjournals.com/content/early/2022/10/13/13993003.01596-2022 https://erj.ersjournals.com/content/early/2022/10/13/13993003.01596-2022.abstract},
volume = {61},
year = {2023}
}

{"_id":"85BjyKF9JYr2ybvub","bibbaseid":"gafar-wasmann-mcilleron-aarnoutse-schaaf-marais-agarwal-antwi-etal-globalestimatesanddeterminantsofantituberculosisdrugpharmacokineticsinchildrenandadolescentsasystematicreviewandindividualpatientdatametaanalysis-2023","author_short":["Gafar, F.","Wasmann, R. E","McIlleron, H. M","Aarnoutse, R. E","Schaaf, H S.","Marais, B. J","Agarwal, D.","Antwi, S.","Bang, N. D","Bekker, A.","Bell, D. J","Chabala, C.","Choo, L.","Davies, G. R","Day, J. N","Dayal, R.","Denti, P.","Donald, P. R","Engidawork, E.","Garcia-Prats, A. J","Gibb, D.","Graham, S. M","Hesseling, A. C","Heysell, S. K","Idris, M. I","Kabra, S. K","Kinikar, A.","Kumar, A. K H.","Kwara, A.","Lodha, R.","Magis-Escurra, C.","Martinez, N.","Mathew, B. S","Mave, V.","Mduma, E.","Mlotha-Mitole, R.","Mpagama, S. G","Mukherjee, A.","Nataprawira, H. M","Peloquin, C. A","Pouplin, T.","Ramachandran, G.","Ranjalkar, J.","Roy, V.","Ruslami, R.","Shah, I.","Singh, Y.","Sturkenboom, M. G G","Svensson, E. M","Swaminathan, S.","Thatte, U.","Thee, S.","Thomas, T. A","Tikiso, T.","Touw, D. J","Turkova, A.","Velpandian, T.","Verhagen, L. M","Winckler, J. L","Yang, H.","Yunivita, V.","Taxis, K.","Stevens, J.","Alffenaar, J. C","Drugs, f. t. G. C. G. f. M. o. P. I. P. D. i. P. o. A."],"bibdata":{"bibtype":"article","type":"article","abstract":"Background Suboptimal exposure to antituberculosis drugs has been associated with unfavourable treatment outcomes. We aimed to investigate estimates and determinants of first-line antituberculosis drug pharmacokinetics in children and adolescents at a global level. Methods We systematically searched MEDLINE, Embase, and Web of Science (1990–2021) for pharmacokinetic studies of first-line antituberculosis drugs in children and adolescents. Individual patient data were obtained from authors of eligible studies. Summary estimates of total/extrapolated area under the plasma concentration-time curve (AUC0–24) and peak plasma concentration (Cmax) were assessed with random-effects models, normalised with current WHO-recommended paediatric doses. Determinants of AUC0–24 and Cmax were assessed with linear mixed-effects models. Results Of 55 eligible studies, individual patient data were available for 39 (71%), including 1628 participants from 12 countries. Geometric means (95% CIs) of steady-state AUC0–24 were summarised for isoniazid (18.7 [15.5−22.6] h˙mg˙L−1), rifampicin (34.4 [29.4−40.3] h˙mg˙L−1), pyrazinamide (375.0 [339.9−413.7] h˙mg˙L−1), and ethambutol (8.0 [6.4−10.0] h˙mg˙L−1). Our multivariate models indicated that younger age (especially \\textless2 years) and HIV-positive status were associated with lower AUC0–24 for all antituberculosis drugs, while severe malnutrition was associated with lower AUC0–24 for isoniazid and pyrazinamide. N-acetyltransferase 2 rapid acetylators had lower isoniazid AUC0–24 and slow acetylators had higher isoniazid AUC0–24 than intermediate acetylators. Determinants of Cmax were generally similar to those for AUC0–24. Conclusion This study provides the most comprehensive estimates of plasma exposures to first-line antituberculosis drugs in children and adolescents. Key determinants of drug exposures were identified. These may be relevant for population-specific dose adjustment or individualised therapeutic drug monitoring. Footnotes This manuscript has recently been accepted for publication in the European Respiratory Journal . It is published here in its accepted form prior to copyediting and typesetting by our production team. After these production processes are complete and the authors have approved the resulting proofs, the article will move to the latest issue of the ERJ online. Please open or download the PDF to view this article. Conflict of interest: HSS reports grants from the NIH/IMPAACT; and honoraria from Ann Lake publications − sponsored by Johnson & Johnson − for an educational publication on the management of MDR-TB in children. Conflict of interest: AB reports grants from IMPAACT, UNITAID; lecture honoraria from Sandoz; support for attending PENTA PIM meeting; and received generic LPV/r, 3TC and ABC for the PETITE study. Conflict of interest: DJB reports support for attending a meeting from ViiV pharmaceuticals; and attendance fees for an Advisory board meeting from ViiV pharmaceuticals. Conflict of interest: LC reports grants from the UKRI MRC DfID Wellcome NIHR Joint Global Health Trials, TB Alliance Support for trial drug purchase, and UKRI COVID-19 Grant Extension Allocation Award. Conflict of interest: PD reports a grant for WHO expert review for TB drugs in children. Conflict of interest: SMG reports participation on a Data Safety Monitoring Board for the TB CHAMP trial; and leadership roles as a co-chair for Guidelines Development Committee of the WHO updated recommendations and consolidated guidelines on child and adolescents TB, and as a core member for the WHO Child and Adolescent TB Working Group. Conflict of interest: SKH reports grants from the NIH, DANIDA, and EDTCP; royalties or licenses from UpToDate; and honoraria for lectures from Henry Stewart Talks. Conflict of interest: AK reports a grant from the NIH/NICHD. Conflict of interest: VM reports grants from the NIH and CDC. Conflict of interest: CAP reports a grant from the NIH. Conflict of interest: VR reports a grant from the Delhi State TB Association; and leadership roles as a member of the Delhi State TB Association and the MAMC TB Committee. Conflict of interest: EMS reports grants from the NWO personal Veni, IMI UNITE4TB consortium, TB Alliance, UNITAID BenefitKids consortium, WHO expert review, NIH support for IMPAACT studies, Blueprint, Probex, ACTG study Clo-FAST, Janssen pharmaceuticals, EDCTP suport PanTB-HM, and Legochem; and leadership of fiduciary roles in ISOP DI&E committee and BenNeLux PMX organizing committee. Conflict of interest: UT reports participation on a Data Safety Monitoring Board for an ICMR TB trial. Conflict of interest: TAT reports grants from the NIH and the University of Virginia. Conflict of interest: DJT reports a grant from Chiesi; consulting fees from Pure IMS and Sanguin; and participation on a Data Safety Monitoring Board for the FORMAT trial. Conflict of interest: AT reports grants from the UKRI MRC DfID Wellcome NIHR Joint Global Health Trials and the MRC Grants for core funding of the Medical Research Council Clinical Trials Unit at the UCL; and TB Alliance Support for SHINE trial drug purchase. Conflict of interest: All of this work was declared by the authors to be outside the submitted work. Conflict of interest: All other authors declare no competing interests.","author":[{"propositions":[],"lastnames":["Gafar"],"firstnames":["Fajri"],"suffixes":[]},{"propositions":[],"lastnames":["Wasmann"],"firstnames":["Roeland","E"],"suffixes":[]},{"propositions":[],"lastnames":["McIlleron"],"firstnames":["Helen","M"],"suffixes":[]},{"propositions":[],"lastnames":["Aarnoutse"],"firstnames":["Rob","E"],"suffixes":[]},{"propositions":[],"lastnames":["Schaaf"],"firstnames":["H","Simon"],"suffixes":[]},{"propositions":[],"lastnames":["Marais"],"firstnames":["Ben","J"],"suffixes":[]},{"propositions":[],"lastnames":["Agarwal"],"firstnames":["Dipti"],"suffixes":[]},{"propositions":[],"lastnames":["Antwi"],"firstnames":["Sampson"],"suffixes":[]},{"propositions":[],"lastnames":["Bang"],"firstnames":["Nguyen","D"],"suffixes":[]},{"propositions":[],"lastnames":["Bekker"],"firstnames":["Adrie"],"suffixes":[]},{"propositions":[],"lastnames":["Bell"],"firstnames":["David","J"],"suffixes":[]},{"propositions":[],"lastnames":["Chabala"],"firstnames":["Chishala"],"suffixes":[]},{"propositions":[],"lastnames":["Choo"],"firstnames":["Louise"],"suffixes":[]},{"propositions":[],"lastnames":["Davies"],"firstnames":["Geraint","R"],"suffixes":[]},{"propositions":[],"lastnames":["Day"],"firstnames":["Jeremy","N"],"suffixes":[]},{"propositions":[],"lastnames":["Dayal"],"firstnames":["Rajeshwar"],"suffixes":[]},{"propositions":[],"lastnames":["Denti"],"firstnames":["Paolo"],"suffixes":[]},{"propositions":[],"lastnames":["Donald"],"firstnames":["Peter","R"],"suffixes":[]},{"propositions":[],"lastnames":["Engidawork"],"firstnames":["Ephrem"],"suffixes":[]},{"propositions":[],"lastnames":["Garcia-Prats"],"firstnames":["Anthony","J"],"suffixes":[]},{"propositions":[],"lastnames":["Gibb"],"firstnames":["Diana"],"suffixes":[]},{"propositions":[],"lastnames":["Graham"],"firstnames":["Stephen","M"],"suffixes":[]},{"propositions":[],"lastnames":["Hesseling"],"firstnames":["Anneke","C"],"suffixes":[]},{"propositions":[],"lastnames":["Heysell"],"firstnames":["Scott","K"],"suffixes":[]},{"propositions":[],"lastnames":["Idris"],"firstnames":["Misgana","I"],"suffixes":[]},{"propositions":[],"lastnames":["Kabra"],"firstnames":["Sushil","K"],"suffixes":[]},{"propositions":[],"lastnames":["Kinikar"],"firstnames":["Aarti"],"suffixes":[]},{"propositions":[],"lastnames":["Kumar"],"firstnames":["Agibothu","K","Hemanth"],"suffixes":[]},{"propositions":[],"lastnames":["Kwara"],"firstnames":["Awewura"],"suffixes":[]},{"propositions":[],"lastnames":["Lodha"],"firstnames":["Rakesh"],"suffixes":[]},{"propositions":[],"lastnames":["Magis-Escurra"],"firstnames":["Cecile"],"suffixes":[]},{"propositions":[],"lastnames":["Martinez"],"firstnames":["Nilza"],"suffixes":[]},{"propositions":[],"lastnames":["Mathew"],"firstnames":["Binu","S"],"suffixes":[]},{"propositions":[],"lastnames":["Mave"],"firstnames":["Vidya"],"suffixes":[]},{"propositions":[],"lastnames":["Mduma"],"firstnames":["Estomih"],"suffixes":[]},{"propositions":[],"lastnames":["Mlotha-Mitole"],"firstnames":["Rachel"],"suffixes":[]},{"propositions":[],"lastnames":["Mpagama"],"firstnames":["Stellah","G"],"suffixes":[]},{"propositions":[],"lastnames":["Mukherjee"],"firstnames":["Aparna"],"suffixes":[]},{"propositions":[],"lastnames":["Nataprawira"],"firstnames":["Heda","M"],"suffixes":[]},{"propositions":[],"lastnames":["Peloquin"],"firstnames":["Charles","A"],"suffixes":[]},{"propositions":[],"lastnames":["Pouplin"],"firstnames":["Thomas"],"suffixes":[]},{"propositions":[],"lastnames":["Ramachandran"],"firstnames":["Geetha"],"suffixes":[]},{"propositions":[],"lastnames":["Ranjalkar"],"firstnames":["Jaya"],"suffixes":[]},{"propositions":[],"lastnames":["Roy"],"firstnames":["Vandana"],"suffixes":[]},{"propositions":[],"lastnames":["Ruslami"],"firstnames":["Rovina"],"suffixes":[]},{"propositions":[],"lastnames":["Shah"],"firstnames":["Ira"],"suffixes":[]},{"propositions":[],"lastnames":["Singh"],"firstnames":["Yatish"],"suffixes":[]},{"propositions":[],"lastnames":["Sturkenboom"],"firstnames":["Marieke","G","G"],"suffixes":[]},{"propositions":[],"lastnames":["Svensson"],"firstnames":["Elin","M"],"suffixes":[]},{"propositions":[],"lastnames":["Swaminathan"],"firstnames":["Soumya"],"suffixes":[]},{"propositions":[],"lastnames":["Thatte"],"firstnames":["Urmila"],"suffixes":[]},{"propositions":[],"lastnames":["Thee"],"firstnames":["Stephanie"],"suffixes":[]},{"propositions":[],"lastnames":["Thomas"],"firstnames":["Tania","A"],"suffixes":[]},{"propositions":[],"lastnames":["Tikiso"],"firstnames":["Tjokosela"],"suffixes":[]},{"propositions":[],"lastnames":["Touw"],"firstnames":["Daan","J"],"suffixes":[]},{"propositions":[],"lastnames":["Turkova"],"firstnames":["Anna"],"suffixes":[]},{"propositions":[],"lastnames":["Velpandian"],"firstnames":["Thirumurthy"],"suffixes":[]},{"propositions":[],"lastnames":["Verhagen"],"firstnames":["Lilly","M"],"suffixes":[]},{"propositions":[],"lastnames":["Winckler"],"firstnames":["Jana","L"],"suffixes":[]},{"propositions":[],"lastnames":["Ya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Respiratory Journal","keywords":"OA,OA_PMC,fund_not_ack,review","mendeley-tags":"OA,OA_PMC,fund_not_ack,review","month":"nov","number":"3","pages":"2201596","pmid":"36328357","publisher":"European Respiratory Society","title":"Global estimates and determinants of antituberculosis drug pharmacokinetics in children and adolescents: a systematic review and individual patient data meta-analysis","url":"https://erj.ersjournals.com/content/early/2022/10/13/13993003.01596-2022 https://erj.ersjournals.com/content/early/2022/10/13/13993003.01596-2022.abstract","volume":"61","year":"2023","bibtex":"@article{Gafar2022,\r\nabstract = {Background Suboptimal exposure to antituberculosis drugs has been associated with unfavourable treatment outcomes. We aimed to investigate estimates and determinants of first-line antituberculosis drug pharmacokinetics in children and adolescents at a global level. Methods We systematically searched MEDLINE, Embase, and Web of Science (1990–2021) for pharmacokinetic studies of first-line antituberculosis drugs in children and adolescents. Individual patient data were obtained from authors of eligible studies. Summary estimates of total/extrapolated area under the plasma concentration-time curve (AUC0–24) and peak plasma concentration (Cmax) were assessed with random-effects models, normalised with current WHO-recommended paediatric doses. Determinants of AUC0–24 and Cmax were assessed with linear mixed-effects models. Results Of 55 eligible studies, individual patient data were available for 39 (71{\\%}), including 1628 participants from 12 countries. Geometric means (95{\\%} CIs) of steady-state AUC0–24 were summarised for isoniazid (18.7 [15.5−22.6] h{\\textperiodcentered}mg{\\textperiodcentered}L−1), rifampicin (34.4 [29.4−40.3] h{\\textperiodcentered}mg{\\textperiodcentered}L−1), pyrazinamide (375.0 [339.9−413.7] h{\\textperiodcentered}mg{\\textperiodcentered}L−1), and ethambutol (8.0 [6.4−10.0] h{\\textperiodcentered}mg{\\textperiodcentered}L−1). Our multivariate models indicated that younger age (especially {\\textless}2 years) and HIV-positive status were associated with lower AUC0–24 for all antituberculosis drugs, while severe malnutrition was associated with lower AUC0–24 for isoniazid and pyrazinamide. N-acetyltransferase 2 rapid acetylators had lower isoniazid AUC0–24 and slow acetylators had higher isoniazid AUC0–24 than intermediate acetylators. Determinants of Cmax were generally similar to those for AUC0–24. Conclusion This study provides the most comprehensive estimates of plasma exposures to first-line antituberculosis drugs in children and adolescents. Key determinants of drug exposures were identified. These may be relevant for population-specific dose adjustment or individualised therapeutic drug monitoring. Footnotes This manuscript has recently been accepted for publication in the European Respiratory Journal . It is published here in its accepted form prior to copyediting and typesetting by our production team. After these production processes are complete and the authors have approved the resulting proofs, the article will move to the latest issue of the ERJ online. Please open or download the PDF to view this article. Conflict of interest: HSS reports grants from the NIH/IMPAACT; and honoraria from Ann Lake publications − sponsored by Johnson {\\&} Johnson − for an educational publication on the management of MDR-TB in children. Conflict of interest: AB reports grants from IMPAACT, UNITAID; lecture honoraria from Sandoz; support for attending PENTA PIM meeting; and received generic LPV/r, 3TC and ABC for the PETITE study. Conflict of interest: DJB reports support for attending a meeting from ViiV pharmaceuticals; and attendance fees for an Advisory board meeting from ViiV pharmaceuticals. Conflict of interest: LC reports grants from the UKRI MRC DfID Wellcome NIHR Joint Global Health Trials, TB Alliance Support for trial drug purchase, and UKRI COVID-19 Grant Extension Allocation Award. Conflict of interest: PD reports a grant for WHO expert review for TB drugs in children. Conflict of interest: SMG reports participation on a Data Safety Monitoring Board for the TB CHAMP trial; and leadership roles as a co-chair for Guidelines Development Committee of the WHO updated recommendations and consolidated guidelines on child and adolescents TB, and as a core member for the WHO Child and Adolescent TB Working Group. Conflict of interest: SKH reports grants from the NIH, DANIDA, and EDTCP; royalties or licenses from UpToDate; and honoraria for lectures from Henry Stewart Talks. Conflict of interest: AK reports a grant from the NIH/NICHD. Conflict of interest: VM reports grants from the NIH and CDC. Conflict of interest: CAP reports a grant from the NIH. Conflict of interest: VR reports a grant from the Delhi State TB Association; and leadership roles as a member of the Delhi State TB Association and the MAMC TB Committee. Conflict of interest: EMS reports grants from the NWO personal Veni, IMI UNITE4TB consortium, TB Alliance, UNITAID BenefitKids consortium, WHO expert review, NIH support for IMPAACT studies, Blueprint, Probex, ACTG study Clo-FAST, Janssen pharmaceuticals, EDCTP suport PanTB-HM, and Legochem; and leadership of fiduciary roles in ISOP DI{\\&}E committee and BenNeLux PMX organizing committee. Conflict of interest: UT reports participation on a Data Safety Monitoring Board for an ICMR TB trial. Conflict of interest: TAT reports grants from the NIH and the University of Virginia. Conflict of interest: DJT reports a grant from Chiesi; consulting fees from Pure IMS and Sanguin; and participation on a Data Safety Monitoring Board for the FORMAT trial. Conflict of interest: AT reports grants from the UKRI MRC DfID Wellcome NIHR Joint Global Health Trials and the MRC Grants for core funding of the Medical Research Council Clinical Trials Unit at the UCL; and TB Alliance Support for SHINE trial drug purchase. Conflict of interest: All of this work was declared by the authors to be outside the submitted work. Conflict of interest: All other authors declare no competing interests.},\r\nauthor = {Gafar, Fajri and Wasmann, Roeland E and McIlleron, Helen M and Aarnoutse, Rob E and Schaaf, H Simon and Marais, Ben J and Agarwal, Dipti and Antwi, Sampson and Bang, Nguyen D and Bekker, Adrie and Bell, David J and Chabala, Chishala and Choo, Louise and Davies, Geraint R and Day, Jeremy N and Dayal, Rajeshwar and Denti, Paolo and Donald, Peter R and Engidawork, Ephrem and Garcia-Prats, Anthony J and Gibb, Diana and Graham, Stephen M and Hesseling, Anneke C and Heysell, Scott K and Idris, Misgana I and Kabra, Sushil K and Kinikar, Aarti and Kumar, Agibothu K Hemanth and Kwara, Awewura and Lodha, Rakesh and Magis-Escurra, Cecile and Martinez, Nilza and Mathew, Binu S and Mave, Vidya and Mduma, Estomih and Mlotha-Mitole, Rachel and Mpagama, Stellah G and Mukherjee, Aparna and Nataprawira, Heda M and Peloquin, Charles A and Pouplin, Thomas and Ramachandran, Geetha and Ranjalkar, Jaya and Roy, Vandana and Ruslami, Rovina and Shah, Ira and Singh, Yatish and Sturkenboom, Marieke G G and Svensson, Elin M and Swaminathan, Soumya and Thatte, Urmila and Thee, Stephanie and Thomas, Tania A and Tikiso, Tjokosela and Touw, Daan J and Turkova, Anna and Velpandian, Thirumurthy and Verhagen, Lilly M and Winckler, Jana L and Yang, Hongmei and Yunivita, Vycke and Taxis, Katja and Stevens, Jasper and Alffenaar, Jan-Willem C and Drugs, for the Global Collaborative Group for Meta-Analysis of Paediatric Individual Patient Data in Pharmacokinetics of Anti-TB},\r\ndoi = {10.1183/13993003.01596-2022},\r\nissn = {0903-1936},\r\njournal = {European Respiratory Journal},\r\nkeywords = {OA,OA{\\_}PMC,fund{\\_}not{\\_}ack,review},\r\nmendeley-tags = {OA,OA{\\_}PMC,fund{\\_}not{\\_}ack,review},\r\nmonth = {nov},\r\nnumber = {3},\r\npages = {2201596},\r\npmid = {36328357},\r\npublisher = {European Respiratory Society},\r\ntitle = {{Global estimates and determinants of antituberculosis drug pharmacokinetics in children and adolescents: a systematic review and individual patient data meta-analysis}},\r\nurl = {https://erj.ersjournals.com/content/early/2022/10/13/13993003.01596-2022 https://erj.ersjournals.com/content/early/2022/10/13/13993003.01596-2022.abstract},\r\nvolume = {61},\r\nyear = {2023}\r\n}\r\n","author_short":["Gafar, F.","Wasmann, R. E","McIlleron, H. M","Aarnoutse, R. E","Schaaf, H S.","Marais, B. J","Agarwal, D.","Antwi, S.","Bang, N. D","Bekker, A.","Bell, D. J","Chabala, C.","Choo, L.","Davies, G. R","Day, J. N","Dayal, R.","Denti, P.","Donald, P. R","Engidawork, E.","Garcia-Prats, A. J","Gibb, D.","Graham, S. M","Hesseling, A. C","Heysell, S. K","Idris, M. I","Kabra, S. K","Kinikar, A.","Kumar, A. K H.","Kwara, A.","Lodha, R.","Magis-Escurra, C.","Martinez, N.","Mathew, B. S","Mave, V.","Mduma, E.","Mlotha-Mitole, R.","Mpagama, S. G","Mukherjee, A.","Nataprawira, H. M","Peloquin, C. A","Pouplin, T.","Ramachandran, G.","Ranjalkar, J.","Roy, V.","Ruslami, R.","Shah, I.","Singh, Y.","Sturkenboom, M. G G","Svensson, E. M","Swaminathan, S.","Thatte, U.","Thee, S.","Thomas, T. A","Tikiso, T.","Touw, D. J","Turkova, A.","Velpandian, T.","Verhagen, L. M","Winckler, J. L","Yang, H.","Yunivita, V.","Taxis, K.","Stevens, J.","Alffenaar, J. C","Drugs, f. t. G. C. G. f. M. o. P. I. P. D. i. P. o. 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