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Low levels of pyrazinamide and ethambutol in children with tuberculosis and impact of age, nutritional status, and human immunodeficiency virus infection

Graham, S. M., Bell, David J., Nyirongo, S., Hartkoorn, R., Ward, Steve ORCID: https://orcid.org/0000-0003-2331-3192 and Molyneux, Malcolm E (2006) 'Low levels of pyrazinamide and ethambutol in children with tuberculosis and impact of age, nutritional status, and human immunodeficiency virus infection'. Antimicrobial Agents and Chemotherapy, Vol 50, Issue 2, pp. 407-413.

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Abstract

Recent pharmacokinetic studies that included children found that serum drug levels were low compared to those of adults for whom the same dosages were used. This study aimed to characterize the pharmacokinetics of pyrazinamide and ethambutol in Malawian children and to examine the impact of age, nutritional status, and human immunodeficiency virus (HIV) infection. We conducted a pharmacokinetic study of children treated for tuberculosis with thrice-weekly pyrazinamide (n = 27; mean age, 5.7 years) and of a separate group of children treated with thrice-weekly ethambutol (n = 18; mean age, 5.5 years) as portions of tablets according to national guidelines. Malnutrition and HIV infection were common in both groups. Blood samples were taken just prior to oral administration of the first dose, and subsequent samples were taken at intervals of 2, 3, 4, 7, 24, and 48 h after drug administration. Serum drug levels were low in all children for both drugs; in almost all cases, the maximum concentration of the drug in serum (C-max failed to reach the MIC for Mycobacterium tuberculosis. The C-max of pyrazinamide was significantly lower in younger children (< 5 years) than in older children. The C-max of pyrazinamide was also lower for HIV-infected children and children with severe malnutrition, but these differences did not reach statistical significance. No differences were found for ethambutol in relation to age, HIV infection, or malnutrition, but the C-max was < 2 mg/liter in all cases. Studies of pharmacokinetic parameters and clinical outcomes obtained by using higher dosages of drugs for treatment of childhood tuberculosis are needed, and recommended dosages may need to be increased.

Item Type: Article
Subjects: WC Communicable Diseases > Virus Diseases > Acquired Immunodeficiency Syndrome. HIV Infections > WC 503 Acquired immunodeficiency syndrome. HIV infections
WC Communicable Diseases > Virus Diseases > Acquired Immunodeficiency Syndrome. HIV Infections > WC 503.5 Complications
WF Respiratory System > Tuberculosis > WF 200 Tuberculosis (General)
WF Respiratory System > Tuberculosis > WF 205.1 General coverage
WF Respiratory System > Tuberculosis > WF 300 Pulmonary tuberculosis
WF Respiratory System > Tuberculosis > WF 415 Tuberculosis in childhood
WS Pediatrics > Diseases of Children and Adolescents > General Diseases > WS 200 General works
WS Pediatrics > Diseases of Children and Adolescents > By System > WS 280 Respiratory system
Faculty: Department: Groups (2002 - 2012) > Child & Reproductive Health Group
Groups (2002 - 2012) > Molecular & Biochemical Parasitology Group
Digital Object Identifer (DOI): https://doi.org/10.1128/AAC.50.2.407-413.2006
Depositing User: Sarah Lewis-Newton
Date Deposited: 24 Feb 2011 11:07
Last Modified: 06 Feb 2018 13:01
URI: http://archive.lstmed.ac.uk/id/eprint/1491

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