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Population Pharmaco...
Population Pharmacokinetics and Dosing of Ethionamide in Children with Tuberculosis
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- Bjugård Nyberg, Henrik, 1984- (författare)
- Uppsala universitet,Institutionen för farmaceutisk biovetenskap
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- Draper, Heather R. (författare)
- Stellenbosch Univ, Fac Med & Hlth Sci, Desmond Tutu TB Ctr, Dept Paediat & Child Hlth, Cape Town, South Africa
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- Garcia-Prats, Anthony J. (författare)
- Stellenbosch Univ, Fac Med & Hlth Sci, Desmond Tutu TB Ctr, Dept Paediat & Child Hlth, Cape Town, South Africa
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- Thee, Stephanie (författare)
- Charite, Dept Pediat, Div Pneumonol Immunol & Intens Care, Berlin, Germany
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- Bekker, Adrie (författare)
- Stellenbosch Univ, Fac Med & Hlth Sci, Desmond Tutu TB Ctr, Dept Paediat & Child Hlth, Cape Town, South Africa
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- Zar, Heather J. (författare)
- Red Cross War Mem Childrens Hosp, Dept Paediat & Child Hlth, Cape Town, South Africa;Univ Cape Town, MRC, Unit Child & Adolescent Hlth, Cape Town, South Africa
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- Hooker, Andrew C., 1973- (författare)
- Uppsala universitet,Institutionen för farmaceutisk biovetenskap
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- Schaaf, H. Simon (författare)
- Stellenbosch Univ, Fac Med & Hlth Sci, Desmond Tutu TB Ctr, Dept Paediat & Child Hlth, Cape Town, South Africa
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- McIlleron, Helen (författare)
- Univ Cape Town, Dept Med, Div Clin Pharmacol, Cape Town, South Africa
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- Hesseling, Anneke C. (författare)
- Stellenbosch Univ, Fac Med & Hlth Sci, Desmond Tutu TB Ctr, Dept Paediat & Child Hlth, Cape Town, South Africa
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- Denti, Paolo (författare)
- Univ Cape Town, Dept Med, Div Clin Pharmacol, Cape Town, South Africa
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(creator_code:org_t)
- American Society for Microbiology, 2020
- 2020
- Engelska.
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Ingår i: Antimicrobial Agents and Chemotherapy. - : American Society for Microbiology. - 0066-4804 .- 1098-6596. ; 64:3
- 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
- Ethionamide has proven efficacy against both drug-susceptible and some drug-resistant strains of Mycobacterium tuberculosis. Limited information on its pharmacokinetics in children is available, and current doses are extrapolated from weight-based adult doses. Pediatric doses based on more robust evidence are expected to improve antituberculosis treatment, especially in small children. In this analysis, ethionamide concentrations in children from 2 observational clinical studies conducted in Cape Town, South Africa, were pooled. All children received ethionamide once daily at a weight-based dose of approximately 20 mg/kg of body weight (range, 10.4 to 25.3 mg/kg) in combination with other first- or second-line antituberculosis medications and with antiretroviral therapy in cases of HIV coinfection. Pharmacokinetic parameters were estimated using nonlinear mixed-effects modeling. The MDR-PK1 study contributed data for 110 children on treatment for multidrug-resistant tuberculosis, while the DATiC study contributed data for 9 children treated for drug-susceptible tuberculosis. The median age of the children in the studies combined was 2.6 years (range, 0.23 to 15 years), and the median weight was 12.5 kg (range, 2.5 to 66 kg). A one-compartment, transit absorption model with first-order elimination best described ethionamide pharmacokinetics in children. Allometric scaling of clearance (typical value, 8.88 liters/h), the volume of distribution (typical value, 21.4 liters), and maturation of clearance and absorption improved the model fit. HIV coinfection decreased the ethionamide bioavailability by 22%, rifampin coadministration increased clearance by 16%, and ethionamide administration by use of a nasogastric tube increased the rate, but the not extent, of absorption. The developed model was used to predict pediatric doses achieving the same drug exposure achieved in 50- to 70-kg adults receiving 750-mg once-daily dosing. Based on model predictions, we recommend a weight-banded pediatric dosing scheme using scored 125-mg tablets.
Ämnesord
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Farmaceutiska vetenskaper (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Pharmaceutical Sciences (hsv//eng)
Nyckelord
- ethionamide
- multidrug resistance
- pediatric infectious disease
- population pharmacokinetics
- tuberculosis
Publikations- och innehållstyp
- ref (ämneskategori)
- art (ämneskategori)
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Bjugård Nyberg, ...
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Draper, Heather ...
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Garcia-Prats, An ...
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Thee, Stephanie
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Bekker, Adrie
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Zar, Heather J.
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Hooker, Andrew C ...
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Schaaf, H. Simon
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McIlleron, Helen
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Hesseling, Annek ...
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Denti, Paolo
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