Global estimates and determinants of antituberculosis drug pharmacokinetics in children and adolescents: a systematic review and individual patient data meta-analysis.
| Title: | Global estimates and determinants of antituberculosis drug pharmacokinetics in children and adolescents: a systematic review and individual patient data meta-analysis. |
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| Authors: | Gafar F; University of Groningen, Groningen Research Institute of Pharmacy, Unit of PharmacoTherapy, -Epidemiology and -Economics, Groningen, The Netherlands f.gafar@rug.nl.; Wasmann RE; University of Cape Town, Department of Medicine, Division of Clinical Pharmacology, Cape Town, South Africa.; McIlleron HM; University of Cape Town, Department of Medicine, Division of Clinical Pharmacology, Cape Town, South Africa.; University of Cape Town, Institute of Infectious Disease and Molecular Medicine, Wellcome Centre for Infectious Diseases Research in Africa (CIDRI-Africa), Cape Town, South Africa.; Aarnoutse RE; Radboud University Medical Center, Radboud Institute of Health Sciences, Department of Pharmacy, Nijmegen, The Netherlands.; Schaaf HS; Stellenbosch University, Faculty of Medicine and Health Sciences, Department of Paediatrics and Child Health, Desmond Tutu Tuberculosis Centre, Tygerberg, South Africa.; Marais BJ; The Children's Hospital at Westmead, Sydney, Australia.; The University of Sydney, Sydney Institute for Infectious Diseases, Sydney, Australia.; Agarwal D; Ram Manohar Lohia Institute of Medical Sciences, Department of Paediatrics, Lucknow, India.; Antwi S; Komfo Anokye Teaching Hospital, Department of Child Health, Kumasi, Ghana.; Kwame Nkrumah University of Science and Technology, School of Medical Sciences, Department of Child Health, Kumasi, Ghana.; Bang ND; Pham Ngoc Thach Hospital, Ho Chi Minh City, Vietnam.; Bekker A; Stellenbosch University, Faculty of Medicine and Health Sciences, Department of Paediatrics and Child Health, Desmond Tutu Tuberculosis Centre, Tygerberg, South Africa.; Bell DJ; NHS Greater Glasgow and Clyde, Infectious Diseases Unit, Glasgow, UK.; Chabala C; University of Cape Town, Department of Medicine, Division of Clinical Pharmacology, Cape Town, South Africa.; University of Zambia, School of Medicine, Department of Paediatrics, Lusaka, Zambia.; University Teaching Hospitals - Children's Hospital, Lusaka, Zambia.; Choo L; University College London, Medical Research Council Clinical Trials Unit, London, UK.; Davies GR; Malawi Liverpool Wellcome Clinical Research Programme, Clinical Department, Blantyre, Malawi.; University of Liverpool, Institute of Infection, Veterinary and Ecological Sciences, Liverpool, UK.; Day JN; Oxford University Clinical Research Unit, Ho Chi Minh City, Vietnam.; University of Oxford, Nuffield Department of Medicine, Centre for Tropical Medicine and Global Health, Oxford, UK.; Dayal R; Sarojini Naidu Medical College, Department of Pediatrics, Agra, India.; Denti P; University of Cape Town, Department of Medicine, Division of Clinical Pharmacology, Cape Town, South Africa.; Donald PR; Stellenbosch University, Faculty of Medicine and Health Sciences, Department of Paediatrics and Child Health, Desmond Tutu Tuberculosis Centre, Tygerberg, South Africa.; Engidawork E; Addis Ababa University, College of Health Sciences, School of Pharmacy, Department of Pharmacology and Clinical Pharmacy, Addis Ababa, Ethiopia.; Garcia-Prats AJ; Stellenbosch University, Faculty of Medicine and Health Sciences, Department of Paediatrics and Child Health, Desmond Tutu Tuberculosis Centre, Tygerberg, South Africa.; University of Wisconsin-Madison, School of Medicine and Public Health, Department of Pediatrics, Madison, WI, USA.; Gibb D; University College London, Medical Research Council Clinical Trials Unit, London, UK.; Graham SM; University of Melbourne, Department of Paediatrics and Murdoch Children's Research Institute, Royal Children's Hospital, Melbourne, Australia.; International Union Against Tuberculosis and Lung Disease, Paris, France.; Hesseling AC; Stellenbosch University, Faculty of Medicine and Health Sciences, Department of Paediatrics and Child Health, Desmond Tutu Tuberculosis Centre, Tygerberg, South Africa.; Heysell SK; University of Virginia, Division of Infectious Diseases and International Health, Charlottesville, VA, USA.; Idris MI; University of Alabama at Birmingham, Department of Biology, Birmingham, AL, USA.; Kabra SK; All India Institute of Medical Sciences, Departments of Pediatrics, New Delhi, India.; Kinikar A; Byramjee Jeejeebhoy Government Medical College - Johns Hopkins University Clinical Research Site, Pune, India.; Kumar AKH; Indian Council of Medical Research, National Institute for Research in Tuberculosis, Chennai, India.; Kwara A; University of Florida, Emerging Pathogens Institute, College of Medicine, Gainesville, FL, USA.; Lodha R; All India Institute of Medical Sciences, Departments of Pediatrics, New Delhi, India.; Magis-Escurra C; Radboud University Medical Center - TB Expert Centre, Nijmegen, The Netherlands.; Martinez N; Instituto Nacional de Enfermedades Respiratorias y Del Ambiente, Asunción, Paraguay.; Mathew BS; Christian Medical College and Hospital, Department of Pharmacology and Clinical Pharmacology, Vellore, India.; Mave V; Byramjee Jeejeebhoy Government Medical College - Johns Hopkins University Clinical Research Site, Pune, India.; Johns Hopkins University, Department of Medicine and Infectious Diseases, Baltimore, MD, USA.; Mduma E; Haydom Lutheran Hospital, Center for Global Health Research, Haydom, Tanzania.; Mlotha-Mitole R; Queen Elizabeth Central Hospital, Department of Paediatrics, Blantyre, Malawi.; Mpagama SG; Kibong'oto Infectious Diseases Hospital, Sanya Juu, Tanzania.; Mukherjee A; All India Institute of Medical Sciences, Departments of Pediatrics, New Delhi, India.; Nataprawira HM; Universitas Padjadjaran, Hasan Sadikin Hospital, Faculty of Medicine, Department of Child Health, Division of Paediatric Respirology, Bandung, Indonesia.; Peloquin CA; University of Florida College of Pharmacy, Gainesville, FL, USA.; Pouplin T; Mahidol University, Faculty of Tropical Medicine, Mahidol-Oxford Tropical Medicine Research Unit, Bangkok, Thailand.; Ramachandran G; Indian Council of Medical Research, National Institute for Research in Tuberculosis, Chennai, India.; Ranjalkar J; Christian Medical College and Hospital, Department of Pharmacology and Clinical Pharmacology, Vellore, India.; Roy V; Maulana Azad Medical College, Department of Pharmacology, New Delhi, India.; Ruslami R; Universitas Padjadjaran, Faculty of Medicine, Department of Biomedical Sciences, Division of Pharmacology and Therapy, Bandung, Indonesia.; Shah I; Bai Jerbai Wadia Hospital for Children, Department of Pediatric Infectious Diseases, Pediatric TB Clinic, Mumbai, India.; Singh Y; Sarojini Naidu Medical College, Department of Pediatrics, Agra, India.; Sturkenboom MGG; University of Groningen, University Medical Center Groningen, Department of Clinical Pharmacy and Pharmacology, Groningen, The Netherlands.; Svensson EM; Radboud University Medical Center, Radboud Institute of Health Sciences, Department of Pharmacy, Nijmegen, The Netherlands.; Uppsala University, Department of Pharmacy, Uppsala, Sweden.; Swaminathan S; Indian Council of Medical Research, National Institute for Research in Tuberculosis, Chennai, India.; World Health Organization, Public Health Division, Geneva, Switzerland.; Thatte U; Seth Gordhandas Sunderdas Medical College and King Edward Memorial Hospital, Department of Clinical Pharmacology, Mumbai, India.; Thee S; Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, Department of Pediatric Respiratory Medicine, Immunology and Critical Care Medicine, Berlin, Germany.; Thomas TA; University of Virginia, Division of Infectious Diseases and International Health, Charlottesville, VA, USA.; Tikiso T; University of Cape Town, Department of Medicine, Division of Clinical Pharmacology, Cape Town, South Africa.; Touw DJ; University of Groningen, University Medical Center Groningen, Department of Clinical Pharmacy and Pharmacology, Groningen, The Netherlands.; Turkova A; University College London, Medical Research Council Clinical Trials Unit, London, UK.; Velpandian T; All India Institute of Medical Sciences, Ocular Pharmacology and Pharmacy Division, Dr R.P. Centre, New Delhi, India.; Verhagen LM; Radboud University Medical Center, Radboud Center for Infectious Diseases, Laboratory of Medical Immunology, Section of Pediatric Infectious Diseases, Nijmegen, The Netherlands.; Radboud University Medical Center, Amalia Children's Hospital, Department of Paediatric Infectious Diseases and Immunology, Nijmegen, The Netherlands.; Stellenbosch University, Family Centre for Research with UBUNTU, Department of Paediatrics and Child Health, Cape Town, South Africa.; Winckler JL; Stellenbosch University, Faculty of Medicine and Health Sciences, Department of Paediatrics and Child Health, Desmond Tutu Tuberculosis Centre, Tygerberg, South Africa.; Yang H; University of Rochester, School of Medicine and Dentistry, Department of Biostatistics and Computational Biology, Rochester, NY, USA.; Yunivita V; Universitas Padjadjaran, Faculty of Medicine, Department of Biomedical Sciences, Division of Pharmacology and Therapy, Bandung, Indonesia.; Taxis K; University of Groningen, Groningen Research Institute of Pharmacy, Unit of PharmacoTherapy, -Epidemiology and -Economics, Groningen, The Netherlands.; Stevens J; University of Groningen, University Medical Center Groningen, Department of Clinical Pharmacy and Pharmacology, Groningen, The Netherlands.; Both authors contributed equally and shared senior authorship.; Alffenaar JC; The University of Sydney, Sydney Institute for Infectious Diseases, Sydney, Australia.; The University of Sydney, Faculty of Medicine and Health, School of Pharmacy, Sydney, Australia.; Westmead Hospital, Sydney, Australia.; Both authors contributed equally and shared senior authorship. |
| Corporate Authors: | Global Collaborative Group for Meta-Analysis of Paediatric Individual Patient Data in Pharmacokinetics of Anti-TB Drugs |
| Source: | The European respiratory journal [Eur Respir J] 2023 Mar 09; Vol. 61 (3). Date of Electronic Publication: 2023 Mar 09 (Print Publication: 2023). |
| Publication Type: | Systematic Review; Meta-Analysis; Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't |
| Language: | English |
| Journal Info: | Publisher: European Respiratory Society Country of Publication: England NLM ID: 8803460 Publication Model: Electronic-Print Cited Medium: Internet ISSN: 1399-3003 (Electronic) Linking ISSN: 09031936 NLM ISO Abbreviation: Eur Respir J Subsets: MEDLINE |
| Imprint Name(s): | Publication: Sheffield, United Kingdom : European Respiratory Society; Original Publication: Copenhagen : Published jointly by the Society and Munksgaard, 1988- |
| MeSH Terms: | Antitubercular Agents*/therapeutic use ; Isoniazid*/therapeutic use; Pyrazinamide/therapeutic use ; Ethambutol/therapeutic use ; Rifampin/therapeutic use ; Child ; Adolescent ; Humans ; Child, Preschool |
| Abstract: | Background: Suboptimal exposure to antituberculosis (anti-TB) drugs has been associated with unfavourable treatment outcomes. We aimed to investigate estimates and determinants of first-line anti-TB 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 anti-TB 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 from 0 to 24 h post-dose (AUC0-24) and peak plasma concentration (C max) were assessed with random-effects models, normalised with current World Health Organization-recommended paediatric doses. Determinants of AUC0-24 and C max 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 of steady-state AUC0-24 were summarised for isoniazid (18.7 (95% CI 15.5-22.6) h·mg·L-1), rifampicin (34.4 (95% CI 29.4-40.3) h·mg·L-1), pyrazinamide (375.0 (95% CI 339.9-413.7) h·mg·L-1) and ethambutol (8.0 (95% CI 6.4-10.0) h·mg·L-1). Our multivariate models indicated that younger age (especially |
| Competing Interests: | Conflict of interest: H.S. Schaaf 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. A. Bekker 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. D.J. Bell reports support for attending a meeting from ViiV pharmaceuticals; and attendance fees for an advisory board meeting from ViiV pharmaceuticals. L. Choo 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. P. Denti reports a grant for WHO expert review for TB drugs in children. S.M. Graham reports participation on a data safety monitoring board for the TB CHAMP trial; and leadership roles as a co-chair for the Guidelines Development Committee of the WHO updated recommendations and consolidated guidelines on child and adolescent TB, and as a core member for the WHO Child and Adolescent TB Working Group. S.K. Heysell reports grants from the NIH, DANIDA and EDTCP; royalties or licences from UpToDate; and honoraria for lectures from Henry Stewart Talks. A. Kwara reports a grant from the NIH/NICHD. V. Mave reports grants from the NIH and CDC. C.A. Peloquin reports a grant from the NIH. V. Roy 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. E.M. Svensson 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 support PanTB-HM and Legochem; and leadership or fiduciary roles in the ISOP DI&E committee and BenNeLux PMX organising committee. U. Thatte reports participation on a data safety monitoring board for an ICMR TB trial. T.A. Thomas reports grants from the NIH and the University of Virginia. D.J. Touw reports a grant from Chiesi; consulting fees from Pure IMS and Sanguin; and participation on a data safety monitoring board for the FORMAT trial. A. Turkova reports grants from the UKRI MRC DFID Wellcome NIHR Joint Global Health Trials and 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. All of this work was declared by the authors to be outside the submitted work. All other authors declare no competing interests. |
| Comments: | Comment in: Eur Respir J. 2023 Mar 9;61(3):2202003. doi: 10.1183/13993003.02003-2022.. (PMID: 36894189) |
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| Grant Information: | MR/L004445/1 United Kingdom MRC_ Medical Research Council; MC_UU_12023/27 United Kingdom MRC_ Medical Research Council; MC_UU_12023/26 United Kingdom MRC_ Medical Research Council; U01 AI115594 United States AI NIAID NIH HHS; United Kingdom WT_ Wellcome Trust; R01 HD069175 United States HD NICHD NIH HHS; 001 International WHO_ World Health Organization; R01 AI037845 United States AI NIAID NIH HHS; R01 HD071779 United States HD NICHD NIH HHS; R01 AI137080 United States AI NIAID NIH HHS; M01 RR000051 United States RR NCRR NIH HHS; K23 AI097197 United States AI NIAID NIH HHS; MC_UU_00004/04 United Kingdom MRC_ Medical Research Council |
| Substance Nomenclature: | 0 (Antitubercular Agents); V83O1VOZ8L (Isoniazid); 2KNI5N06TI (Pyrazinamide); 8G167061QZ (Ethambutol); VJT6J7R4TR (Rifampin) |
| Entry Date(s): | Date Created: 20221103 Date Completed: 20230313 Latest Revision: 20250626 |
| Update Code: | 20260130 |
| PubMed Central ID: | PMC9996834 |
| DOI: | 10.1183/13993003.01596-2022 |
| PMID: | 36328357 |
| Database: | MEDLINE |
Systematic Review; Meta-Analysis; Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't