H McIlleron1, H Hundt1, W Smythe2, A Bekker3, J Winckler4, L van der Laan3, P Smith1, H J Zar5, A C Hesseling3, G Maartens1, L Wiesner1, A van Rie6. 1. Division of Clinical Pharmacology, Department of Medicine, University of Cape Town, Cape Town, South Africa. 2. Division of Clinical Pharmacology, Department of Medicine, Clinical Research Centre, Health Sciences Faculty, University of Cape Town, Cape Town, South Africa. 3. Desmond Tutu TB Centre, Department of Paediatrics and Child Health, Faculty of Medicine and Health Sciences, Stellenbosch University, Cape Town, South Africa. 4. Department of Paediatrics and Child Health, and Medical Research Council Unit on Child and Adolescent Health, University of Cape Town, Cape Town, South Africa. 5. Department of Paediatrics and Child Health, and Medical Research Council Unit on Child and Adolescent Health, University of Cape Town, Cape Town, South Africa; Red Cross War Memorial Children's Hospital, Cape Town, South Africa. 6. Department of Epidemiology, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA; International Health Unit, Epidemiology and Social Medicine, Faculty of Medicine, University of Antwerp, Antwerp, Belgium.
Abstract
SETTING: To assess the revised World Health Organization-recommended dose of 10-20 mg/kg rifampicin (RMP), we studied the steady state pharmacokinetics of RMP in South African children who received standard treatment for drug-susceptible tuberculosis (TB). OBJECTIVE: To determine the formulation effect on the pharmacokinetics of RMP. DESIGN: RMP plasma concentrations were characterised in 146 children (median age 1.4 years, range 0.2-10.2). The morning dose on the day of the pharmacokinetic evaluation was administered as one of two RMP single-drug oral suspensions. RESULTS: While one formulation achieved 2 h concentrations in the range of those observed in adults (median 6.54 mg/l, interquartile range [IQR] 4.47-8.84), the other attained a median bioavailability of only 25% of this, with a median 2 h concentration of 1.59 mg/l (IQR 0.89-2.38). CONCLUSION: RMP is a key drug for the treatment of TB. It is critical that the quality of RMP suspensions used to treat childhood TB is ensured.
SETTING: To assess the revised World Health Organization-recommended dose of 10-20 mg/kg rifampicin (RMP), we studied the steady state pharmacokinetics of RMP in South African children who received standard treatment for drug-susceptible tuberculosis (TB). OBJECTIVE: To determine the formulation effect on the pharmacokinetics of RMP. DESIGN:RMP plasma concentrations were characterised in 146 children (median age 1.4 years, range 0.2-10.2). The morning dose on the day of the pharmacokinetic evaluation was administered as one of two RMP single-drug oral suspensions. RESULTS: While one formulation achieved 2 h concentrations in the range of those observed in adults (median 6.54 mg/l, interquartile range [IQR] 4.47-8.84), the other attained a median bioavailability of only 25% of this, with a median 2 h concentration of 1.59 mg/l (IQR 0.89-2.38). CONCLUSION:RMP is a key drug for the treatment of TB. It is critical that the quality of RMP suspensions used to treat childhood TB is ensured.
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