Naïve-Pooled pharmacokinetic analysis of pyrazinamide, isoniazid and rifampicin in plasma and cerebrospinal fluid of Vietnamese children with tuberculous meningitisReport as inadecuate




Naïve-Pooled pharmacokinetic analysis of pyrazinamide, isoniazid and rifampicin in plasma and cerebrospinal fluid of Vietnamese children with tuberculous meningitis - Download this document for free, or read online. Document in PDF available to download.

Reference: Pouplin, Thomas, Bang, ND, Toi, PV et al., (2016). Naïve-Pooled pharmacokinetic analysis of pyrazinamide, isoniazid and rifampicin in plasma and cerebrospinal fluid of Vietnamese children with tuberculous meningitis. BMC Infectious Diseases, 16, Article: 144.Citable link to this page:

 

Naïve-Pooled pharmacokinetic analysis of pyrazinamide, isoniazid and rifampicin in plasma and cerebrospinal fluid of Vietnamese children with tuberculous meningitis

Abstract: Among the various forms of TB, tuberculous meningitis (TBM) is the most severe, with about 30 % mortality and 50 % of survivors left with neurological sequelae. Children suffer more frequently from TBM than adults and outcomes are often poor due to difficulties in making the diagnosis and uncertainty regarding the best anti-tuberculosis drug regimen. The aim of this prospective study was to describe the pharmacokinetics of pyrazinamide, isoniazid and rifampicin in plasma and cerebrospinal fluid of children with tuberculous meningitis treated with the standard TBM regimen.We performed a prospective observational study of 100 consecutively treated children (≤15 years of age) with tuberculous meningitis in Ho Chi Minh City, Vietnam. Children were treated according to the 2006 WHO recommended pediatric treatment regimen consisting of isoniazid (5 mg/kg), rifampicin (10 mg/kg) and ethambutol (15 mg/kg) for 8 months, with the addition of pyrazinamide (25 mg/kg) for the first 3 months and streptomycin (15 mg/kg) for the first 2 months. Pyrazinamide, isoniazid and rifampicin concentrations were measured in plasma at day 14 and in cerebrospinal fluid (CSF) at 1 month by HPLC-UV. A naïve-pooled non-compartmental data analysis was used to describe the pharmacokinetic properties of drugs in the two-age groups of children ≤ 4 years or > 4 years of age.Results:Younger children, when compared to older children, presented a higher body weight-normalized clearance and volume of distribution, and lower median total plasma exposures for the three studied drugs with −14 %, −22 % and −16 % for Pyrazinamide, Isoniazid and Rifampicin, respectively. In CSF, individual concentrations of isoniazid and pyrazinamide were comparable to that in plasma in both age groups; but rifampicin concentrations were lower than the minimum inhibitory concentration of susceptible bacteria in all but two children.Conclusions:There is an age-dependent variation in the plasma and cerebrospinal fluid pharmacokinetics of rifampicin, isoniazid and pyrazinamide. The safety and efficacy of higher doses of rifampicin should be investigated for the treatment of childhood tuberculous meningitis.

Publication status:PublishedPeer Review status:Peer reviewedVersion:Publisher's version Funder: Wellcome Trust   Notes:Copyright © 2016 Pouplin et al. Open Access This article is distributed under the terms of the Creative Commons Attribution 4.0International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, andreproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link tothe Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver(http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.

Bibliographic Details

Publisher: BioMed Central

Publisher Website: https://www.biomedcentral.com/

Journal: BMC Infectious Diseasessee more from them

Publication Website: https://bmcinfectdis.biomedcentral.com/

Volume: 16

Extent: Article: 144

Issue Date: 2016

pages:Article: 144Identifiers

Urn: uuid:a9ee7425-e797-482a-8c8c-50ba931801aa

Issn: 1471-2334

Source identifier: 612713

Doi: https://doi.org/10.1186/s12879-016-1470-x Item Description

Type: Journal article;

Version: Publisher's versionKeywords: TB meningitis children pharmacokinetics Rifampicin anti-tuberculosis drugs HPLC Tiny URL: pubs:612713

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Author: Pouplin, Thomas - institutionUniversity of Oxford Oxford, MSD, NDM, Tropical Medicine - - - Bang, ND - - - Toi, PV - - - Phuong,

Source: https://ora.ox.ac.uk/objects/uuid:a9ee7425-e797-482a-8c8c-50ba931801aa



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