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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Global estimates and determinants of antituberculosis drug pharmacokinetics in children and adolescents : a systematic review and individual patient data meta-analysis

Gafar, Fajri (author): Univ Groningen, Groningen Res Inst Pharm, Unit PharmacoTherapy Epidemiol & Econ, Groningen, Netherlands.

Wasmann, Roeland E. (author): Univ Cape Town, Div Clin Pharmacol, Dept Med, Cape Town, South Africa.

McIlleron, Helen M. (author): Univ Cape Town, Div Clin Pharmacol, Dept Med, Cape Town, South Africa.;Univ Cape Town, Inst Infect Dis & Mol Med, Wellcome Ctr Infect Dis Res Africa CIDRI Africa, Cape Town, South Africa.

Aarnoutse, Rob E. (author): Radboud Univ Nijmegen, Radboud Inst Hlth Sci, Dept Pharm, Med Ctr, Nijmegen, Netherlands.

Schaaf, H. Simon (author): Stellenbosch Univ, Dept Paediat & Child Hlth, Desmond Tutu TB Ctr, Fac Med & Hlth Sci, Tygerberg, South Africa.

Marais, Ben J. (author): Childrens Hosp Westmead, Sydney, NSW, Australia.;Univ Sydney, Sydney Inst Infect Dis, Sydney, NSW, Australia.

Agarwal, Dipti (author): Ram Manohar Lohia Inst Med Sci, Dept Paediat, Lucknow, Uttar Pradesh, India.

Antwi, Sampson (author): Komfo Anokye Teaching Hosp, Dept Child Hlth, Kumasi, Ghana.;Kwame Nkrumah Univ Sci & Technol, Sch Med Sci, Dept Child Hlth, Kumasi, Ghana.

Bang, Nguyen D. (author): Pham Ngoc Thach Hosp, Ho Chi Minh City, Vietnam.

Bekker, Adrie (author): Stellenbosch Univ, Dept Paediat & Child Hlth, Desmond Tutu TB Ctr, Fac Med & Hlth Sci, Tygerberg, South Africa.

Bell, David J. (author): NHS Greater Glasgow & Clyde, Infect Dis Unit, Glasgow, Lanark, Scotland.

Chabala, Chishala (author): Univ Cape Town, Div Clin Pharmacol, Dept Med, Cape Town, South Africa.;Univ Zambia, Sch Med, Dept Paediat, Lusaka, Zambia.;Childrens Hosp, Univ Teaching Hosp, Lusaka, Zambia.

Choo, Louise (author): UCL, Med Res Council, Clin Trials Unit, London, England.

Davies, Geraint R. (author): Malawi Liverpool Wellcome Clin Res Programme, Clin Dept, Blantyre, Malawi.;Univ Liverpool, Inst Infect Vet & Ecol Sci, Liverpool, Merseyside, England.

Day, Jeremy N. (author): Univ Oxford, Clin Res Unit, Ho Chi Minh City, Vietnam.;Univ Oxford, Nuffield Dept Med, Ctr Trop Med & Global Hlth, Oxford, England.

Dayal, Rajeshwar (author): Sarojini Naidu Med Coll, Dept Pediat, Agra, Uttar Pradesh, India.

Denti, Paolo (author): Univ Cape Town, Div Clin Pharmacol, Dept Med, Cape Town, South Africa.

Donald, Peter R. (author): Stellenbosch Univ, Dept Paediat & Child Hlth, Desmond Tutu TB Ctr, Fac Med & Hlth Sci, Tygerberg, South Africa.

Engidawork, Ephrem (author): Addis Ababa Univ, Sch Pharm, Dept Pharmacol & Clin Pharm, Coll Hlth Sci, Addis Ababa, Ethiopia.

Garcia-Prats, Anthony J. (author): Stellenbosch Univ, Dept Paediat & Child Hlth, Desmond Tutu TB Ctr, Fac Med & Hlth Sci, Tygerberg, South Africa.;Univ Wisconsin, Sch Med & Publ Hlth, Dept Pediat, Madison, WI USA.

Gibb, Diana (author): UCL, Med Res Council, Clin Trials Unit, London, England.

Graham, Stephen M. (author): Univ Melbourne, Dept Pediat, Melbourne, Vic, Australia.;Royal Childrens Hosp, Murdoch Childrens Res Inst, Melbourne, Vic, Australia.;Int Union TB & Lung Dis, Paris, France.

Hesseling, Anneke C. (author): Stellenbosch Univ, Dept Paediat & Child Hlth, Desmond Tutu TB Ctr, Fac Med & Hlth Sci, Tygerberg, South Africa.

Heysell, Scott K. (author): Univ Virginia, Div Infect Dis & Int Hlth, Charlottesville, VA USA.

Idris, Misgana I. (author): Univ Alabama Birmingham, Dept Biol, Birmingham, AL 35294 USA.

Kabra, Sushil K. (author): All India Inst Med Sci, Dept Pediat, New Delhi, India.

Kinikar, Aarti (author): Johns Hopkins Univ, Byramjee Jeejeebhoy Govt Med Coll, Clinical Res Site, Pune, Maharashtra, India.

Kumar, Agibothu K. Hemanth (author): Indian Council Med Res, Natl Inst Res TB, Chennai, Tamil Nadu, India.

Kwara, Awewura (author): Univ Florida, Emerging Pathogens Inst, Coll Med, Gainesville, FL USA.

Lodha, Rakesh (author): All India Inst Med Sci, Dept Pediat, New Delhi, India.

Magis-Escurra, Cecile (author): Radboud Univ Nijmegen, Med Ctr, TB Expert Ctr, Nijmegen, Netherlands.

Martinez, Nilza (author): Inst Nacl Enfermedades Resp & Ambiente, Asuncion, Paraguay.

Mathew, Binu S. (author): Christian Med Coll & Hosp, Dept Pharmacol & Clin Pharmacol, Vellore, Tamil Nadu, India.

Mave, Vidya (author): Johns Hopkins Univ, Byramjee Jeejeebhoy Govt Med Coll, Clinical Res Site, Pune, Maharashtra, India.;Johns Hopkins Univ, Dept Med & Infect Dis, Baltimore, MD USA.

Mduma, Estomih (author): Haydom Lutheran Hosp, Ctr Global Hlth Res, Haydom, Tanzania.

Mlotha-Mitole, Rachel (author): Queen Elizabeth Cent Hosp, Dept Paediat, Blantyre, Malawi.

Mpagama, Stellah G. (author): Kibongoto Infect Dis Hosp, Sanya Juu, Tanzania.

Mukherjee, Aparna (author): All India Inst Med Sci, Dept Pediat, New Delhi, India.

Nataprawira, Heda M. (author): Univ Padjadjaran, Hasan Sadikin Hosp, Div Paediat Respirol, Dept Child Hlth,Fac Med, Bandung, Indonesia.

Peloquin, Charles A. (author): Univ Florida, Coll Pharm, Gainesville, FL USA.

Pouplin, Thomas (author): Mahidol Univ, Fac Trop Med, Mahidol Oxford Trop Med Res Unit, Bangkok, Thailand.

Ramachandran, Geetha (author): Indian Council Med Res, Natl Inst Res TB, Chennai, Tamil Nadu, India.

Ranjalkar, Jaya (author): Christian Med Coll & Hosp, Dept Pharmacol & Clin Pharmacol, Vellore, Tamil Nadu, India.

Roy, Vandana (author): Maulana Azad Med Coll, Dept Pharmacol, New Delhi, India.

Ruslami, Rovina (author): Univ Padjadjaran, Div Pharmacol & Therapy, Dept Biomed Sci, Fac Med, Bandung, Indonesia.

Shah, Ira (author): Bai Jerbai Wadia Hosp Children, Dept Pediat Infect Dis, Pediat TB Clin, Mumbai, Maharashtra, India.

Singh, Yatish (author): Sarojini Naidu Med Coll, Dept Pediat, Agra, Uttar Pradesh, India.

Sturkenboom, Marieke G. G. (author): Univ Groningen, Univ Med Ctr Groningen, Dept Clin Pharm & Pharmacol, Groningen, Netherlands.

Svensson, Elin M., 1985- (author): Uppsala universitet,Institutionen för farmaci,Radboud Univ Nijmegen, Radboud Inst Hlth Sci, Dept Pharm, Med Ctr, Nijmegen, Netherlands

Swaminathan, Soumya (author): Indian Council Med Res, Natl Inst Res TB, Chennai, Tamil Nadu, India.;World Hlth Org, Publ Hlth Div, Geneva, Switzerland.

Thatte, Urmila (author): Seth Gordhandas Sunderdas Med Coll & King Edward, Dept Clin Pharmacol, Mumbai, Maharashtra, India.

Thee, Stephanie (author): Charite Univ Med Berlin, Berlin, Germany.;Free Univ Berlin, Berlin, Germany.;Humboldt Univ, Dept Pediat Resp Med Immunol & Crit Care Med, Berlin, Germany.

Thomas, Tania A. (author): Univ Virginia, Div Infect Dis & Int Hlth, Charlottesville, VA USA.

Tikiso, Tjokosela (author): Univ Cape Town, Div Clin Pharmacol, Dept Med, Cape Town, South Africa.

Touw, Daan J. (author): Univ Groningen, Univ Med Ctr Groningen, Dept Clin Pharm & Pharmacol, Groningen, Netherlands.

Turkova, Anna (author): UCL, Med Res Council, Clin Trials Unit, London, England.

Velpandian, Thirumurthy (author): All India Inst Med Sci, Dr RP Ctr, Ocular Pharmacol & Pharm Div, New Delhi, India.

Verhagen, Lilly M. (author): Radboud Univ Nijmegen, Med Ctr, Radboud Ctr Infect Dis, Lab Med Immunol,Sect Pediat Infect Dis, Nijmegen, Netherlands.;Radboud Univ Nijmegen, Med Ctr, Amalia Childrens Hosp, Dept Paediat Infect Dis & Immunol, Nijmegen, Netherlands.;Stellenbosch Univ, Family Ctr Res, UBUNTU, Dept Paediat & Child Hlth, Cape Town, South Africa.

Winckler, Jana L. (author): Stellenbosch Univ, Dept Paediat & Child Hlth, Desmond Tutu TB Ctr, Fac Med & Hlth Sci, Tygerberg, South Africa.

Yang, Hongmei (author): Univ Rochester, Sch Med & Dent, Dept Biostat & Computat Biol, Rochester, NY USA.

Yunivita, Vycke (author): Univ Padjadjaran, Div Pharmacol & Therapy, Dept Biomed Sci, Fac Med, Bandung, Indonesia.

Taxis, Katja (author): Univ Groningen, Groningen Res Inst Pharm, Unit PharmacoTherapy Epidemiol & Econ, Groningen, Netherlands.

Stevens, Jasper (author): Univ Groningen, Univ Med Ctr Groningen, Dept Clin Pharm & Pharmacol, Groningen, Netherlands.

Alffenaar, Jan-Willem C. (author): Univ Sydney, Sydney Inst Infect Dis, Sydney, NSW, Australia.;Univ Sydney, Sch Pharm, Fac Med & Hlth, Sydney, NSW, Australia.;Westmead Hosp, Sydney, NSW, Australia.

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Univ Groningen, Groningen Res Inst Pharm, Unit PharmacoTherapy Epidemiol & Econ, Groningen, Netherlands Univ Cape Town, Div Clin Pharmacol, Dept Med, Cape Town, South Africa. (creator_code:org_t)

2022-11-03
2023
English.
In: European Respiratory Journal. - : European Respiratory Society. - 0903-1936 .- 1399-3003. ; 61:3

Related links:: https://doi.org/10.1...; show more...; https://uu.diva-port... (primary) (Raw object); https://urn.kb.se/re...; https://doi.org/10.1...; show less...

Research review (peer-reviewed)

Abstract Subject headings

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.

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By the author/editor: Gafar, Fajri; Wasmann, Roeland ...; McIlleron, Helen ...; Aarnoutse, Rob E ...; Schaaf, H. Simon; Marais, Ben J.; show more...; Agarwal, Dipti; Antwi, Sampson; Bang, Nguyen D.; Bekker, Adrie; Bell, David J.; Chabala, Chishal ...; Choo, Louise; Davies, Geraint ...; Day, Jeremy N.; Dayal, Rajeshwar; Denti, Paolo; Donald, Peter R.; Engidawork, Ephr ...; Garcia-Prats, An ...; Gibb, Diana; Graham, Stephen ...; Hesseling, Annek ...; Heysell, Scott K ...; Idris, Misgana I ...; Kabra, Sushil K.; Kinikar, Aarti; Kumar, Agibothu ...; Kwara, Awewura; Lodha, Rakesh; Magis-Escurra, C ...; Martinez, Nilza; Mathew, Binu S.; Mave, Vidya; Mduma, Estomih; Mlotha-Mitole, R ...; Mpagama, Stellah ...; Mukherjee, Aparn ...; Nataprawira, Hed ...; Peloquin, Charle ...; Pouplin, Thomas; Ramachandran, Ge ...; Ranjalkar, Jaya; Roy, Vandana; Ruslami, Rovina; Shah, Ira; Singh, Yatish; Sturkenboom, Mar ...; Svensson, Elin M ...; Swaminathan, Sou ...; Thatte, Urmila; Thee, Stephanie; Thomas, Tania A.; Tikiso, Tjokosel ...; Touw, Daan J.; Turkova, Anna; Velpandian, Thir ...; Verhagen, Lilly ...; Winckler, Jana L ...; Yang, Hongmei; Yunivita, Vycke; Taxis, Katja; Stevens, Jasper; Alffenaar, Jan-W ...; show less...

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MEDICAL AND HEALTH SCIENCES: MEDICAL AND HEAL ...; and Basic Medicine; and Pharmaceutical S ...

Articles in the publication: European Respira ...

By the university: Uppsala University

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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

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