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Optimizing Dosing a...
Optimizing Dosing and Fixed-Dose Combinations of Rifampicin, Isoniazid, and Pyrazinamide in Pediatric Patients With Tuberculosis : A Prospective Population Pharmacokinetic Study
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- Denti, Paolo (författare)
- Univ Cape Town, Div Clin Pharmacol, Dept Med, Cape Town, South Africa.
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- Wasmann, Roeland E. (författare)
- Univ Cape Town, Div Clin Pharmacol, Dept Med, Cape Town, South Africa.
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- van Rie, Annelies (författare)
- Univ Antwerp, Family Med & Populat Hlth, Fac Med, Antwerp, Belgium.
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- Winckler, Jana (författare)
- Stellenbosch Univ, Dept Paediat & Child Hlth, Desmond Tutu TB Ctr, Fac Med & Hlth Sci, Cape Town, South Africa.
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- Bekker, Adrie (författare)
- Stellenbosch Univ, Dept Paediat & Child Hlth, Desmond Tutu TB Ctr, Fac Med & Hlth Sci, Cape Town, South Africa.
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- Rabie, Helena (författare)
- Stellenbosch Univ, Dept Paediat & Child Hlth, Cape Town, South Africa.;Stellenbosch Univ, FAMily Ctr Res Ubuntu FAMCRU, Cape Town, South Africa.;Tygerberg Hosp, Cape Town, South Africa.
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- Hesseling, Anneke C. (författare)
- Stellenbosch Univ, Dept Paediat & Child Hlth, Desmond Tutu TB Ctr, Fac Med & Hlth Sci, Cape Town, South Africa.
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- van der Laan, Louvina E. (författare)
- Univ Cape Town, Div Clin Pharmacol, Dept Med, Cape Town, South Africa.;Stellenbosch Univ, Dept Paediat & Child Hlth, Desmond Tutu TB Ctr, Fac Med & Hlth Sci, Cape Town, South Africa.
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- Gonzalez-Martinez, Carmen (författare)
- Malawi Liverpool Wellcome Trust Clin Res Programm, Blantyre, Malawi.;Univ Liverpool Liverpool Sch Trop Med, Liverpool, Merseyside, England.
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- Zar, Heather J. (författare)
- Univ Cape Town, Red Cross War Mem Childrens Hosp, Dept Paediat & Child Hlth, Cape Town, South Africa.;Univ Cape Town, SAMRC Unit Child & Adolescent Hlth, Cape Town, South Africa.
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- Davies, Gerry (författare)
- Univ Liverpool, Inst Translat Med, Dept Mol & Clin Pharmacol, Liverpool, Merseyside, England.;Univ Liverpool, Inst Infect & Global Hlth, Dept Clin Infect Microbiol & Immunol, Liverpool, Merseyside, England.
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- Wiesner, Lubbe (författare)
- Univ Cape Town, Div Clin Pharmacol, Dept Med, Cape Town, South Africa.
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- Svensson, Elin, 1985- (författare)
- Uppsala universitet,Institutionen för farmaceutisk biovetenskap,Institutionen för farmaci,Radboud Univ Nijmegen, Radboud Inst Hlth Sci, Dept Pharm, Med Ctr, Nijmegen, Netherlands.;Uppsala Univ, Dept Pharm, Uppsala, Sweden.
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- McIlleron, Helen M. (författare)
- 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.
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Univ Cape Town, Div Clin Pharmacol, Dept Med, Cape Town, South Africa Univ Antwerp, Family Med & Populat Hlth, Fac Med, Antwerp, Belgium. (creator_code:org_t)
- 2021-10-19
- 2022
- Engelska.
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Ingår i: Clinical Infectious Diseases. - : OXFORD UNIV PRESS INC. - 1058-4838 .- 1537-6591. ; 75:1, s. 141-151
- Relaterad länk:
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https://urn.kb.se/re...
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https://doi.org/10.1...
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Abstract
Ämnesord
Stäng
- Background In 2010, the World Health Organization (WHO) revised dosing guidelines for treatment of childhood tuberculosis. Our aim was to investigate first-line antituberculosis drug exposures under these guidelines, explore dose optimization using the current dispersible fixed-dose combination (FDC) tablet of rifampicin/isoniazid/pyrazinamide; 75/50/150 mg, and suggest a new FDC with revised weight bands. Methods Children with drug-susceptible tuberculosis in Malawi and South Africa underwent pharmacokinetic sampling while receiving first-line tuberculosis drugs as single formulations according the 2010 WHO recommended doses. Nonlinear mixed-effects modeling and simulation was used to design the optimal FDC and weight-band dosing strategy for achieving the pharmacokinetic targets based on literature-derived adult AUC(0-24h) for rifampicin (38.7-72.9), isoniazid (11.6-26.3), and pyrazinamide (233-429 mg center dot h/L). Results In total, 180 children (42% female; 13.9% living with human immunodeficiency virus [HIV]; median [range] age 1.9 [0.22-12] years; weight 10.7 [3.20-28.8] kg) were administered 1, 2, 3, or 4 FDC tablets (rifampicin/isoniazid/pyrazinamide 75/50/150 mg) daily for 4-8, 8-12, 12-16, and 16-25 kg weight bands, respectively. Rifampicin exposure (for weight and age) was up to 50% lower than in adults. Increasing the tablet number resulted in adequate rifampicin but relatively high isoniazid and pyrazinamide exposures. Administering 1, 2, 3, or 4 optimized FDC tablets (rifampicin/isoniazid/pyrazinamide 120/35/130 mg) to children < 6, 6-13, 13-20. and 20-25 kg, and 0.5 tablet in < 3-month-olds with immature metabolism, improved exposures to all 3 drugs. Conclusions Current pediatric FDC doses resulted in low rifampicin exposures. Optimal dosing of all drugs cannot be achieved with the current FDCs. We propose a new FDC formulation and revised weight bands. Current pediatric dosing guidelines lead to infant rifampicin exposures much lower than in adults, whereas isoniazid and pyrazinamide exposures are similar. A new fixed-dose combination (FDC) with rifampicin/isoniazid/pyrazinamide 120/35/130 mg and weight bands of < 6, 6-13, 13-20, and 20-25 kg could improve treatment.
Ämnesord
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Farmaceutiska vetenskaper (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Pharmaceutical Sciences (hsv//eng)
Nyckelord
- children
- first-line tuberculosis treatment
- fixed-dose combination
- NONMEM
- pharmacokinetics
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- ref (ämneskategori)
- art (ämneskategori)
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Denti, Paolo
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Wasmann, Roeland ...
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van Rie, Annelie ...
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Winckler, Jana
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Bekker, Adrie
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Rabie, Helena
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Hesseling, Annek ...
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van der Laan, Lo ...
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Gonzalez-Martine ...
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Zar, Heather J.
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Davies, Gerry
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Wiesner, Lubbe
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Svensson, Elin, ...
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McIlleron, Helen ...
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