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Global estimates and determinants of antituberculosis drug pharmacokinetics in children and adolescents: a systematic review and individual patient data meta-analysis.
Gafar, Fajri; Wasmann, Roeland E; McIlleron, Helen M; Aarnoutse, Rob E; Schaaf, H Simon; Marais, Ben J; Agarwal, Dipti; Antwi, Sampson; Bang, Nguyen D; Bekker, Adrie; Bell, David J; Chabala, Chishala; Choo, Louise; Davies, Geraint R; Day, Jeremy N; Dayal, Rajeshwar; Denti, Paolo; Donald, Peter R; Engidawork, Ephrem; Garcia-Prats, Anthony J; Gibb, Diana; Graham, Stephen M; Hesseling, Anneke C; Heysell, Scott K; Idris, Misgana I; Kabra, Sushil K; Kinikar, Aarti; Kumar, Agibothu K Hemanth; Kwara, Awewura; Lodha, Rakesh; Magis-Escurra, Cecile; Martinez, Nilza; Mathew, Binu S; Mave, Vidya; Mduma, Estomih; Mlotha-Mitole, Rachel; Mpagama, Stellah G; Mukherjee, Aparna; Nataprawira, Heda M; Peloquin, Charles A; Pouplin, Thomas; Ramachandran, Geetha; Ranjalkar, Jaya; Roy, Vandana; Ruslami, Rovina; Shah, Ira; Singh, Yatish; Sturkenboom, Marieke G G; Svensson, Elin M; Swaminathan, Soumya.
Affiliation
  • 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.
  • Aarnoutse RE; 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.
  • Schaaf HS; Radboud University Medical Center, Radboud Institute of Health Sciences, Department of Pharmacy, Nijmegen, The Netherlands.
  • Marais BJ; Stellenbosch University, Faculty of Medicine and Health Sciences, Department of Paediatrics and Child Health, Desmond Tutu Tuberculosis Centre, Tygerberg, South Africa.
  • Agarwal D; The Children's Hospital at Westmead, Sydney, Australia.
  • Antwi S; The University of Sydney, Sydney Institute for Infectious Diseases, Sydney, Australia.
  • Bang ND; Ram Manohar Lohia Institute of Medical Sciences, Department of Paediatrics, Lucknow, India.
  • Bekker A; Komfo Anokye Teaching Hospital, Department of Child Health, Kumasi, Ghana.
  • Bell DJ; Kwame Nkrumah University of Science and Technology, School of Medical Sciences, Department of Child Health, Kumasi, Ghana.
  • Chabala C; Pham Ngoc Thach Hospital, Ho Chi Minh City, Vietnam.
  • Choo L; Stellenbosch University, Faculty of Medicine and Health Sciences, Department of Paediatrics and Child Health, Desmond Tutu Tuberculosis Centre, Tygerberg, South Africa.
  • Davies GR; NHS Greater Glasgow and Clyde, Infectious Diseases Unit, Glasgow, UK.
  • Day JN; University of Cape Town, Department of Medicine, Division of Clinical Pharmacology, Cape Town, South Africa.
  • Dayal R; University of Zambia, School of Medicine, Department of Paediatrics, Lusaka, Zambia.
  • Denti P; University Teaching Hospitals - Children's Hospital, Lusaka, Zambia.
  • Donald PR; University College London, Medical Research Council Clinical Trials Unit, London, UK.
  • Engidawork E; Malawi Liverpool Wellcome Clinical Research Programme, Clinical Department, Blantyre, Malawi.
  • Garcia-Prats AJ; University of Liverpool, Institute of Infection, Veterinary and Ecological Sciences, Liverpool, UK.
  • Gibb D; Oxford University Clinical Research Unit, Ho Chi Minh City, Vietnam.
  • Graham SM; University of Oxford, Nuffield Department of Medicine, Centre for Tropical Medicine and Global Health, Oxford, UK.
  • Hesseling AC; Sarojini Naidu Medical College, Department of Pediatrics, Agra, India.
  • Heysell SK; University of Cape Town, Department of Medicine, Division of Clinical Pharmacology, Cape Town, South Africa.
  • Idris MI; Stellenbosch University, Faculty of Medicine and Health Sciences, Department of Paediatrics and Child Health, Desmond Tutu Tuberculosis Centre, Tygerberg, South Africa.
  • Kabra SK; Addis Ababa University, College of Health Sciences, School of Pharmacy, Department of Pharmacology and Clinical Pharmacy, Addis Ababa, Ethiopia.
  • Kinikar A; Stellenbosch University, Faculty of Medicine and Health Sciences, Department of Paediatrics and Child Health, Desmond Tutu Tuberculosis Centre, Tygerberg, South Africa.
  • Kumar AKH; University of Wisconsin-Madison, School of Medicine and Public Health, Department of Pediatrics, Madison, WI, USA.
  • Kwara A; University College London, Medical Research Council Clinical Trials Unit, London, UK.
  • Lodha R; University of Melbourne, Department of Paediatrics and Murdoch Children's Research Institute, Royal Children's Hospital, Melbourne, Australia.
  • Magis-Escurra C; International Union Against Tuberculosis and Lung Disease, Paris, France.
  • Martinez N; Stellenbosch University, Faculty of Medicine and Health Sciences, Department of Paediatrics and Child Health, Desmond Tutu Tuberculosis Centre, Tygerberg, South Africa.
  • Mathew BS; University of Virginia, Division of Infectious Diseases and International Health, Charlottesville, VA, USA.
  • Mave V; University of Alabama at Birmingham, Department of Biology, Birmingham, AL, USA.
  • Mduma E; All India Institute of Medical Sciences, Departments of Pediatrics, New Delhi, India.
  • Mlotha-Mitole R; Byramjee Jeejeebhoy Government Medical College - Johns Hopkins University Clinical Research Site, Pune, India.
  • Mpagama SG; Indian Council of Medical Research, National Institute for Research in Tuberculosis, Chennai, India.
  • Mukherjee A; University of Florida, Emerging Pathogens Institute, College of Medicine, Gainesville, FL, USA.
  • Nataprawira HM; All India Institute of Medical Sciences, Departments of Pediatrics, New Delhi, India.
  • Peloquin CA; Radboud University Medical Center - TB Expert Centre, Nijmegen, The Netherlands.
  • Pouplin T; Instituto Nacional de Enfermedades Respiratorias y Del Ambiente, Asunción, Paraguay.
  • Ramachandran G; Christian Medical College and Hospital, Department of Pharmacology and Clinical Pharmacology, Vellore, India.
  • Ranjalkar J; Byramjee Jeejeebhoy Government Medical College - Johns Hopkins University Clinical Research Site, Pune, India.
  • Roy V; Johns Hopkins University, Department of Medicine and Infectious Diseases, Baltimore, MD, USA.
  • Ruslami R; Haydom Lutheran Hospital, Center for Global Health Research, Haydom, Tanzania.
  • Shah I; Queen Elizabeth Central Hospital, Department of Paediatrics, Blantyre, Malawi.
  • Singh Y; Kibong'oto Infectious Diseases Hospital, Sanya Juu, Tanzania.
  • Sturkenboom MGG; All India Institute of Medical Sciences, Departments of Pediatrics, New Delhi, India.
  • Svensson EM; Universitas Padjadjaran, Hasan Sadikin Hospital, Faculty of Medicine, Department of Child Health, Division of Paediatric Respirology, Bandung, Indonesia.
  • Swaminathan S; University of Florida College of Pharmacy, Gainesville, FL, USA.
Eur Respir J ; 61(3)2023 03.
Article in En | MEDLINE | ID: mdl-36328357
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 <2 years) and HIV-positive status were associated with lower AUC0-24 for all first-line anti-TB 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 C max were generally similar to those for AUC0-24. CONCLUSIONS: This study provides the most comprehensive estimates of plasma exposures to first-line anti-TB 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.
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Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Isoniazid / Antitubercular Agents Type of study: Systematic_reviews Limits: Adolescent / Child / Child, preschool / Humans Language: En Journal: Eur Respir J Year: 2023 Type: Article Affiliation country: Netherlands
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Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Isoniazid / Antitubercular Agents Type of study: Systematic_reviews Limits: Adolescent / Child / Child, preschool / Humans Language: En Journal: Eur Respir J Year: 2023 Type: Article Affiliation country: Netherlands