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Pharmacokinetics of isoniazid, rifampin, and pyrazinamide in children younger than two years of age with tuberculosis: evidence for implementation of revised World Health Organization recommendations.
Antimicrob Agents Chemother. 2011 Dec; 55(12):5560-7.AA

Abstract

The World Health Organization (WHO) recently issued revised first-line antituberculosis (anti-TB) drug dosage recommendations for children. No pharmacokinetic studies for these revised dosages are available for children <2 years. The aim of the study was to document the pharmacokinetics of the first-line anti-TB agents in children <2 years of age comparing previous and revised WHO dosages of isoniazid (INH; 5 versus 10 mg/kg/day), rifampin (RMP; 10 versus 15 mg/kg/day), and pyrazinamide (PZA; 25 versus 35 mg/kg/day) and to investigate the effects of clinical covariates, including HIV coinfection, nutritional status, age, gender, and type of tuberculosis (TB), and the effect of NAT2 acetylator status. Serum INH, PZA, and RMP levels were prospectively assessed in 20 children <2 years of age treated for TB following the previous and the revised WHO dosage recommendations. Samples were taken prior to dosing and at 0.5, 1.5, 3, and 5 h following dosing. The maximum drug concentration in serum (C(max)), the time to C(max) (t(max)), and the area under the concentration-time curve (AUC) were calculated. Eleven children had pulmonary and 9 had extrapulmonary TB. Five were HIV infected. The mean C(max) (μg/ml) following the administration of previous/revised dosages were as follows: INH, 3.19/8.11; RMP, 6.36/11.69; PZA, 29.94/47.11. The mean AUC (μg·h/ml) were as follows: INH, 8.09/20.36; RMP, 17.78/36.95; PZA, 118.0/175.2. The mean C(max) and AUC differed significantly between doses. There was no difference in the t(max) values achieved. Children less than 2 years of age achieve target concentrations of first-line anti-TB agents using revised WHO dosage recommendations. Our data provided supportive evidence for the implementation of the revised WHO guidelines for first-line anti-TB therapy in young children.

Authors+Show Affiliations

Department of Paediatric Pneumology and Immunology, Charité, Universitätsmedizin Berlin, Germany.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Clinical Trial
Comparative Study
Journal Article

Language

eng

PubMed ID

21968358

Citation

Thee, S, et al. "Pharmacokinetics of Isoniazid, Rifampin, and Pyrazinamide in Children Younger Than Two Years of Age With Tuberculosis: Evidence for Implementation of Revised World Health Organization Recommendations." Antimicrobial Agents and Chemotherapy, vol. 55, no. 12, 2011, pp. 5560-7.
Thee S, Seddon JA, Donald PR, et al. Pharmacokinetics of isoniazid, rifampin, and pyrazinamide in children younger than two years of age with tuberculosis: evidence for implementation of revised World Health Organization recommendations. Antimicrob Agents Chemother. 2011;55(12):5560-7.
Thee, S., Seddon, J. A., Donald, P. R., Seifart, H. I., Werely, C. J., Hesseling, A. C., Rosenkranz, B., Roll, S., Magdorf, K., & Schaaf, H. S. (2011). Pharmacokinetics of isoniazid, rifampin, and pyrazinamide in children younger than two years of age with tuberculosis: evidence for implementation of revised World Health Organization recommendations. Antimicrobial Agents and Chemotherapy, 55(12), 5560-7. https://doi.org/10.1128/AAC.05429-11
Thee S, et al. Pharmacokinetics of Isoniazid, Rifampin, and Pyrazinamide in Children Younger Than Two Years of Age With Tuberculosis: Evidence for Implementation of Revised World Health Organization Recommendations. Antimicrob Agents Chemother. 2011;55(12):5560-7. PubMed PMID: 21968358.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Pharmacokinetics of isoniazid, rifampin, and pyrazinamide in children younger than two years of age with tuberculosis: evidence for implementation of revised World Health Organization recommendations. AU - Thee,S, AU - Seddon,J A, AU - Donald,P R, AU - Seifart,H I, AU - Werely,C J, AU - Hesseling,A C, AU - Rosenkranz,B, AU - Roll,S, AU - Magdorf,K, AU - Schaaf,H S, Y1 - 2011/10/03/ PY - 2011/10/5/entrez PY - 2011/10/5/pubmed PY - 2012/3/30/medline SP - 5560 EP - 7 JF - Antimicrobial agents and chemotherapy JO - Antimicrob. Agents Chemother. VL - 55 IS - 12 N2 - The World Health Organization (WHO) recently issued revised first-line antituberculosis (anti-TB) drug dosage recommendations for children. No pharmacokinetic studies for these revised dosages are available for children <2 years. The aim of the study was to document the pharmacokinetics of the first-line anti-TB agents in children <2 years of age comparing previous and revised WHO dosages of isoniazid (INH; 5 versus 10 mg/kg/day), rifampin (RMP; 10 versus 15 mg/kg/day), and pyrazinamide (PZA; 25 versus 35 mg/kg/day) and to investigate the effects of clinical covariates, including HIV coinfection, nutritional status, age, gender, and type of tuberculosis (TB), and the effect of NAT2 acetylator status. Serum INH, PZA, and RMP levels were prospectively assessed in 20 children <2 years of age treated for TB following the previous and the revised WHO dosage recommendations. Samples were taken prior to dosing and at 0.5, 1.5, 3, and 5 h following dosing. The maximum drug concentration in serum (C(max)), the time to C(max) (t(max)), and the area under the concentration-time curve (AUC) were calculated. Eleven children had pulmonary and 9 had extrapulmonary TB. Five were HIV infected. The mean C(max) (μg/ml) following the administration of previous/revised dosages were as follows: INH, 3.19/8.11; RMP, 6.36/11.69; PZA, 29.94/47.11. The mean AUC (μg·h/ml) were as follows: INH, 8.09/20.36; RMP, 17.78/36.95; PZA, 118.0/175.2. The mean C(max) and AUC differed significantly between doses. There was no difference in the t(max) values achieved. Children less than 2 years of age achieve target concentrations of first-line anti-TB agents using revised WHO dosage recommendations. Our data provided supportive evidence for the implementation of the revised WHO guidelines for first-line anti-TB therapy in young children. SN - 1098-6596 UR - https://www.unboundmedicine.com/medline/citation/21968358/Pharmacokinetics_of_isoniazid_rifampin_and_pyrazinamide_in_children_younger_than_two_years_of_age_with_tuberculosis:_evidence_for_implementation_of_revised_World_Health_Organization_recommendations_ L2 - http://aac.asm.org/cgi/pmidlookup?view=long&amp;pmid=21968358 DB - PRIME DP - Unbound Medicine ER -