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

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 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.