Browsing by Author "Cilliers, Karien"

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    The pharmacokinetics and toxicity of antituberculosis agents and other co-administered drugs in children with tuberculosis, with and without HIV infection, and their relationship to nutritional status
    (Stellenbosch : University of Stellenbosch, 2011-03) Cilliers, Karien; Labadarios, Demetre; Donald, Peter R.; Nel, Daniel G.; University of Stellenbosch. Faculty of Health Sciences. Dept. of Interdisciplinary Health Sciences. Human Nutrition.
    ENGLISH ABSTRACT: Problem definition: Malnutrition increases the incidence and exacerbates the clinical manifestations of TB. Hepatotoxicity is one of the most serious and most frequent side-effects of anti-tuberculosis drugs and may be three times higher in malnourished patients. Objective: The influence of nutritional and retroviral status on the bio-availability and toxicity of anti-tuberculosis agents was studied and a possible relationship between abdominal lymph node enlargement and the occurrence of malnutrition investigated. Subjects and setting: The study subjects were 53 children, 19 HIV-infected and 34 HIV-uninfected, aged 3 months to 13 years with probable or confirmed tuberculosis admitted to the paediatric ward of Brooklyn Hospital for Chest Diseases in Cape Town, South Africa. The nutritional status of the children was assessed over the first four months of tuberculosis treatment by nutrient intake, anthropometric status and biochemical parameters. The relationship between abdominal lymph node enlargement and the occurrence of malnutrition was also evaluated. Pharmacokinetic studies were performed to evaluate the bio-availability of anti-tuberculosis agents and drug hepato-toxicity was evaluated by liver function. Results: Stunting (46.27%) and underweight (34.51%) were the most common types of malnutrition in the children studied. HIV-infection did not have a significant effect on stunting or wasting, but had a significant effect (p=0.003) on underweight for age with 31.5% HIV-infected compared to 2.9% HIV-uninfected at enrolment, but the effect was not statistically significant at month 4. There was no change in the number of stunted, wasted or underweight children from enrolment after 1 month of treatment to month 4 of treatment. HIV-infection did not have a significant effect on abdominal TB involvement (p=0.43354), and nutritional status was not significantly affected by abdominal lymph-node involvement. At enrolment weight for age had a significant effect on AST and ALT with p-values of 0.02166 and 0.02765 respectively and wasting had a significant effect on GGT at enrolment (p=0.03014). However on enrolment only two HIV-infected and two HIV-uninfected children had ALT values increased >X2 normal. Similarly AST values >X3 normal were found in only one HIV-infected child and two HIV-uninfected children. Stunting did not significantly affect liver enzymes. Anthopometric status did not have a significant effect on liver enzymes at month 4. None of the parameters used to determine nutritional status had a statistically significant effect on INH-levels or RMP-levels. HIV-infection had a significant negatve effect on selenium (p=0.030 and 0.012) and ferritin (p=0.026 and 0.002) at enrolment and month 4 and on IBC (p=0.025) at enrolment. At month 4 HIV-infection had a significant negative effect on the mean vitamin C-levels (p=0.005). Conclusions: HIV co-infection did not affect the extent or distribution of body composition changes in this study. Stunting was the most prevalent form of malnutrition in the study group, indicating longstanding undernutrition, which may be due to factors other than the present TB infection. Appropriate treatment of tuberculosis did not appear to affect the nutritional status over the four month period of the study.
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    Rifampin pharmacokinetics in children, with and without human immunodeficiency virus infection, hospitalized for the management of severe forms of tuberculosis
    (2009-04) Schaaf, H. Simon; Willemse, Marianne; Cilliers, Karien; Labadarios, Demetre; Maritz, Johannes Stephanus; Hussey, Gregory D.; McIlleron, Helen; Smith, Peter; Donald, Peter Roderick
    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 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.