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, H. Simonen_ZA
dc.contributor.authorWillemse, Marianneen_ZA
dc.contributor.authorCilliers, Karienen_ZA
dc.contributor.authorLabadarios, Demetreen_ZA
dc.contributor.authorMaritz, Johannes Stephanusen_ZA
dc.contributor.authorHussey, Gregory D.en_ZA
dc.contributor.authorMcIlleron, Helenen_ZA
dc.contributor.authorSmith, Peteren_ZA
dc.contributor.authorDonald, Peter Rodericken_ZA
dc.date.accessioned2010-12-13T10:10:52Z
dc.date.available2010-12-13T10:10:52Z
dc.date.issued2009-04
dc.date.updated2010-11-02T13:10:09Z
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 μg/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 μg/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 μg/ml (P = 0.20) at 1 month after the start of treatment and 4.0 and 4.6 μg/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 μg/ml and even 4 μg/ml Conclusion 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.description.versionPeer Reviewed
dc.format.extent10 p.
dc.identifier.citationSchaaf, HS, Willemse, M, Cilliers, K, Labadarios, D, Maritz, JS, Hussey, GD, McIlleron, H, Smith, P & Donald, PR 2009, 'Rifampin pharmacokinetics in children, with and without human immunodeficiency virus infection, hospitalized for the management of severe forms of tuberculosis', BMC Medicine7(1):19.en_ZA
dc.identifier.issn1741-7015
dc.identifier.otherhttp://dx.doi.org/10.1186/1741-7015-7-19
dc.identifier.urihttp://hdl.handle.net/10019.1/5064
dc.language.isoen_USen_ZA
dc.language.rfc3066en
dc.rights.holderSchaaf et al.; licensee BioMed Central Ltd.en_ZA
dc.subjectRifampinen_ZA
dc.subjectAnti-tuberculosis chemotherapyen_ZA
dc.subjectHIV and AIDSen_ZA
dc.subjectTuberculosis in children -- Chemotherapyen_ZA
dc.titleRifampin pharmacokinetics in children, with and without human immunodeficiency virus infection, hospitalized for the management of severe forms of tuberculosisen_ZA
dc.typeArticleen_ZA
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