Rifampin pharmacokinetics in children, with and without human immunodeficiency virus infection, hospitalized for the management of severe forms of tuberculosis

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dc.contributor.authorSchaaf, Hendrik Sen_ZA
dc.contributor.authorWillemse, Marianneen_ZA
dc.contributor.authorCilliers, Karienen_ZA
dc.contributor.authorLabadarios, Demetreen_ZA
dc.contributor.authorMaritz, Johannes Sen_ZA
dc.contributor.authorHussey, Gregory Den_ZA
dc.contributor.authorMcIlleron, Helenen_ZA
dc.contributor.authorSmith, Peteren_ZA
dc.contributor.authorDonald, Peter Ren_ZA
dc.date.accessioned2015-11-04T11:55:00Z
dc.date.available2015-11-04T11:55:00Z
dc.date.issued2009en_ZA
dc.description.abstractBACKGROUND: Rifampin is a key drug in antituberculosis chemotherapy because it rapidly kills the majority of bacilli in tuberculosis lesions, prevents relapse and thus enables 6-month short-course chemotherapy. Little is known about the pharmacokinetics of rifampin in children. The objective of this study was to evaluate the pharmacokinetics of rifampin in children with tuberculosis, both human immunodeficiency virus type-1-infected and human immunodeficiency virus-uninfected. METHODS: Fifty-four children, 21 human immunodeficiency virus-infected and 33 human immunodeficiency virus-uninfected, mean ages 3.73 and 4.05 years (P = 0.68), respectively, admitted to a tuberculosis hospital in Cape Town, South Africa with severe forms of tuberculosis were studied approximately 1 month and 4 months after commencing antituberculosis treatment. Blood specimens for analysis were drawn in the morning, 45 minutes, 1.5, 3.0, 4.0 and 6.0 hours after dosing. Rifampin concentrations were determined by liquid chromatography tandem mass spectrometry. For two sample comparisons of means, the Welch version of the t-test was used; associations between variables were examined by Pearson correlation and by multiple linear regression. RESULTS: The children received a mean rifampin dosage of 9.61 mg/kg (6.47 to 15.58) body weight at 1 month and 9.63 mg/kg (4.63 to 17.8) at 4 months after commencing treatment administered as part of a fixed-dose formulation designed for paediatric use. The mean rifampin area under the curve 0 to 6 hours after dosing was 14.9 and 18.1 mug/hour/ml (P = 0.25) 1 month after starting treatment in human immunodeficiency virus-infected and human immunodeficiency virus-uninfected children, respectively, and 16.52 and 17.94 mug/hour/ml (P = 0.59) after 4 months of treatment. The mean calculated 2-hour rifampin concentrations in these human immunodeficiency virus-infected and human immunodeficiency virus-uninfected children were 3.9 and 4.8 mug/ml (P = 0.20) at 1 month after the start of treatment and 4.0 and 4.6 mug/ml (P = 0.33) after 4 months of treatment. These values are considerably less than the suggested lower limit for 2-hour rifampin concentrations in adults of 8.0 mug/ml and even 4 mug/mlCONCLUSION:Both human immunodeficiency virus-infected and human immunodeficiency virus-uninfected children with tuberculosis have very low rifampin serum concentrations after receiving standard rifampin dosages similar to those used in adults. Pharmacokinetic studies of higher dosages of rifampin are urgently needed in children to assist in placing the dosage of rifampin used in childhood on a more scientific foundation.en_ZA
dc.identifier.apacitationSchaaf, H. S., Willemse, M., Cilliers, K., Labadarios, D., Maritz, J. S., Hussey, G. D., ... Donald, P. R. (2009). Rifampin pharmacokinetics in children, with and without human immunodeficiency virus infection, hospitalized for the management of severe forms of tuberculosis. <i>BMC Medicine</i>, http://hdl.handle.net/11427/14676en_ZA
dc.identifier.chicagocitationSchaaf, Hendrik S, Marianne Willemse, Karien Cilliers, Demetre Labadarios, Johannes S Maritz, Gregory D Hussey, Helen McIlleron, Peter Smith, and Peter R Donald "Rifampin pharmacokinetics in children, with and without human immunodeficiency virus infection, hospitalized for the management of severe forms of tuberculosis." <i>BMC Medicine</i> (2009) http://hdl.handle.net/11427/14676en_ZA
dc.identifier.citationSchaaf, H. S., Willemse, M., Cilliers, K., Labadarios, D., Maritz, J. S., Hussey, G. D., ... & Donald, P. R. (2009). Rifampin pharmacokinetics in children, with and without human immunodeficiency virus infection, hospitalized for the management of severe forms of tuberculosis. BMC medicine, 7(1), 19.en_ZA
dc.identifier.ris TY - Journal Article AU - Schaaf, Hendrik S AU - Willemse, Marianne AU - Cilliers, Karien AU - Labadarios, Demetre AU - Maritz, Johannes S AU - Hussey, Gregory D AU - McIlleron, Helen AU - Smith, Peter AU - Donald, Peter R AB - BACKGROUND: Rifampin is a key drug in antituberculosis chemotherapy because it rapidly kills the majority of bacilli in tuberculosis lesions, prevents relapse and thus enables 6-month short-course chemotherapy. Little is known about the pharmacokinetics of rifampin in children. The objective of this study was to evaluate the pharmacokinetics of rifampin in children with tuberculosis, both human immunodeficiency virus type-1-infected and human immunodeficiency virus-uninfected. METHODS: Fifty-four children, 21 human immunodeficiency virus-infected and 33 human immunodeficiency virus-uninfected, mean ages 3.73 and 4.05 years (P = 0.68), respectively, admitted to a tuberculosis hospital in Cape Town, South Africa with severe forms of tuberculosis were studied approximately 1 month and 4 months after commencing antituberculosis treatment. Blood specimens for analysis were drawn in the morning, 45 minutes, 1.5, 3.0, 4.0 and 6.0 hours after dosing. Rifampin concentrations were determined by liquid chromatography tandem mass spectrometry. For two sample comparisons of means, the Welch version of the t-test was used; associations between variables were examined by Pearson correlation and by multiple linear regression. RESULTS: The children received a mean rifampin dosage of 9.61 mg/kg (6.47 to 15.58) body weight at 1 month and 9.63 mg/kg (4.63 to 17.8) at 4 months after commencing treatment administered as part of a fixed-dose formulation designed for paediatric use. The mean rifampin area under the curve 0 to 6 hours after dosing was 14.9 and 18.1 mug/hour/ml (P = 0.25) 1 month after starting treatment in human immunodeficiency virus-infected and human immunodeficiency virus-uninfected children, respectively, and 16.52 and 17.94 mug/hour/ml (P = 0.59) after 4 months of treatment. The mean calculated 2-hour rifampin concentrations in these human immunodeficiency virus-infected and human immunodeficiency virus-uninfected children were 3.9 and 4.8 mug/ml (P = 0.20) at 1 month after the start of treatment and 4.0 and 4.6 mug/ml (P = 0.33) after 4 months of treatment. These values are considerably less than the suggested lower limit for 2-hour rifampin concentrations in adults of 8.0 mug/ml and even 4 mug/mlCONCLUSION:Both human immunodeficiency virus-infected and human immunodeficiency virus-uninfected children with tuberculosis have very low rifampin serum concentrations after receiving standard rifampin dosages similar to those used in adults. Pharmacokinetic studies of higher dosages of rifampin are urgently needed in children to assist in placing the dosage of rifampin used in childhood on a more scientific foundation. DA - 2009 DB - OpenUCT DO - 10.1186/1741-7015-7-19 DP - University of Cape Town J1 - BMC Medicine LK - https://open.uct.ac.za PB - University of Cape Town PY - 2009 T1 - Rifampin pharmacokinetics in children, with and without human immunodeficiency virus infection, hospitalized for the management of severe forms of tuberculosis TI - Rifampin pharmacokinetics in children, with and without human immunodeficiency virus infection, hospitalized for the management of severe forms of tuberculosis UR - http://hdl.handle.net/11427/14676 ER - en_ZA
dc.identifier.urihttp://hdl.handle.net/11427/14676
dc.identifier.urihttp://dx.doi.org/10.1186/1741-7015-7-19
dc.identifier.vancouvercitationSchaaf HS, Willemse M, Cilliers K, Labadarios D, Maritz JS, Hussey GD, et al. Rifampin pharmacokinetics in children, with and without human immunodeficiency virus infection, hospitalized for the management of severe forms of tuberculosis. BMC Medicine. 2009; http://hdl.handle.net/11427/14676.en_ZA
dc.language.isoengen_ZA
dc.publisherBioMed Central Ltden_ZA
dc.publisher.departmentInstitute of Infectious Disease and Molecular Medicineen_ZA
dc.publisher.facultyFaculty of Health Sciencesen_ZA
dc.publisher.institutionUniversity of Cape Town
dc.rightsThis is an Open Access article distributed under the terms of the Creative Commons Attribution Licenseen_ZA
dc.rights.holder2009 Schaaf et al; licensee BioMed Central Ltd.en_ZA
dc.rights.urihttp://creativecommons.org/licenses/by/2.0en_ZA
dc.sourceBMC Medicineen_ZA
dc.source.urihttp://www.biomedcentral.com/bmcmed/en_ZA
dc.subject.otherSmear-positive Pulmonary Tuberculosis, Serum CRP Concentrationen_ZA
dc.subject.otherReverse Transcriptase Inhibitoren_ZA
dc.subject.otherHIV-uninfected Patienten_ZA
dc.subject.otherElevated Serum CRP Concentrationen_ZA
dc.subject.otherBasal Enhancementen_ZA
dc.subject.otherGastric Aspirateen_ZA
dc.subject.otherTuberculen_ZA
dc.titleRifampin pharmacokinetics in children, with and without human immunodeficiency virus infection, hospitalized for the management of severe forms of tuberculosisen_ZA
dc.typeJournal Articleen_ZA
uct.type.filetypeText
uct.type.filetypeImage
uct.type.publicationResearchen_ZA
uct.type.resourceArticleen_ZA
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