Global estimates and determinants of antituberculosis drug pharmacokinetics in children and adolescents: a systematic review and individual patient data meta-analysis
Issued Date
2023-03-01
Resource Type
ISSN
09031936
eISSN
13993003
Scopus ID
2-s2.0-85150001397
Pubmed ID
36328357
Journal Title
European Respiratory Journal
Volume
61
Issue
3
Rights Holder(s)
SCOPUS
Bibliographic Citation
European Respiratory Journal Vol.61 No.3 (2023)
Suggested Citation
Gafar F., Wasmann R.E., McIlleron H.M., Aarnoutse R.E., Simon Schaaf H., 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., Hemanth Kumar A.K., 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.W.C. Global estimates and determinants of antituberculosis drug pharmacokinetics in children and adolescents: a systematic review and individual patient data meta-analysis. European Respiratory Journal Vol.61 No.3 (2023). doi:10.1183/13993003.01596-2022 Retrieved from: https://repository.li.mahidol.ac.th/handle/20.500.14594/82369
Title
Global estimates and determinants of antituberculosis drug pharmacokinetics in children and adolescents: a systematic review and individual patient data meta-analysis
Author(s)
Gafar F.
Wasmann R.E.
McIlleron H.M.
Aarnoutse R.E.
Simon Schaaf H.
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.
Hemanth Kumar A.K.
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.W.C.
Wasmann R.E.
McIlleron H.M.
Aarnoutse R.E.
Simon Schaaf H.
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.
Hemanth Kumar A.K.
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.W.C.
Author's Affiliation
Pham Ngoc Thach Hospital
Mahidol Oxford Tropical Medicine Research Unit
Oxford University Clinical Research Unit
Dr. Rajendra Prasad Centre for Ophthalmic Sciences
University Teaching Hospital Lusaka
University of Zambia School of Medicine
Queen Elizabeth Central Hospital Malawi
Malawi-Liverpool-Wellcome Trust Clinical Research Programme
Kwame Nkrumah University of Science and Technology
Komfo Anokye Teaching Hospital
Haydom Lutheran Hospital
Addis Ababa University
Seth GS Medical College and KEM Hospital
Universitas Padjadjaran
NHS Greater Glasgow and Clyde
Organisation Mondiale de la Santé
The University of Alabama at Birmingham
The Children's Hospital at Westmead
University of Melbourne
Charité – Universitätsmedizin Berlin
The University of Sydney
University of Wisconsin School of Medicine and Public Health
Sanjay Gandhi Postgraduate Institute of Medical Sciences Lucknow
International Union Against Tuberculosis and Lung Disease
University College London
University of Virginia
Tuberculosis Research Centre India
University of Liverpool
University of Florida Academic Health Center
University of Rochester School of Medicine and Dentistry
Faculty of Medicine and Health
Rijksuniversiteit Groningen
All India Institute of Medical Sciences, New Delhi
Maulana Azad Medical College
Nuffield Department of Medicine
University of Florida College of Medicine
Universitair Medisch Centrum Groningen
Johns Hopkins University
Westmead Hospital
Uppsala Universitet
Radboud University Medical Center
Faculty of Medicine and Health Sciences
Stellenbosch University
Bai Jerbai Wadia Hospital for Children
Christian Medical College, Vellore
University of Cape Town
Instituto Nacional de Enfermedades Respiratorias y Del Ambiente
Sarojini Naidu Medical College
Kibong’oto Infectious Diseases Hospital
Mahidol Oxford Tropical Medicine Research Unit
Oxford University Clinical Research Unit
Dr. Rajendra Prasad Centre for Ophthalmic Sciences
University Teaching Hospital Lusaka
University of Zambia School of Medicine
Queen Elizabeth Central Hospital Malawi
Malawi-Liverpool-Wellcome Trust Clinical Research Programme
Kwame Nkrumah University of Science and Technology
Komfo Anokye Teaching Hospital
Haydom Lutheran Hospital
Addis Ababa University
Seth GS Medical College and KEM Hospital
Universitas Padjadjaran
NHS Greater Glasgow and Clyde
Organisation Mondiale de la Santé
The University of Alabama at Birmingham
The Children's Hospital at Westmead
University of Melbourne
Charité – Universitätsmedizin Berlin
The University of Sydney
University of Wisconsin School of Medicine and Public Health
Sanjay Gandhi Postgraduate Institute of Medical Sciences Lucknow
International Union Against Tuberculosis and Lung Disease
University College London
University of Virginia
Tuberculosis Research Centre India
University of Liverpool
University of Florida Academic Health Center
University of Rochester School of Medicine and Dentistry
Faculty of Medicine and Health
Rijksuniversiteit Groningen
All India Institute of Medical Sciences, New Delhi
Maulana Azad Medical College
Nuffield Department of Medicine
University of Florida College of Medicine
Universitair Medisch Centrum Groningen
Johns Hopkins University
Westmead Hospital
Uppsala Universitet
Radboud University Medical Center
Faculty of Medicine and Health Sciences
Stellenbosch University
Bai Jerbai Wadia Hospital for Children
Christian Medical College, Vellore
University of Cape Town
Instituto Nacional de Enfermedades Respiratorias y Del Ambiente
Sarojini Naidu Medical College
Kibong’oto Infectious Diseases Hospital
Other Contributor(s)
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 (Cmax) were assessed with random-effects models, normalised with current World Health Organization-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 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 Cmax 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.