Blood levels of isoniazid in Indian children with tuberculosis

Abstract

Background: Under the Revised National Tuberculosis Control Program (RNTCP) in India children are receiving antituberculosis treatment (ATT) as per a weight band system. In this children may be receiving antituberculosis drugs in doses which may be more or less than that recommended in mg/kg body weight doses. The recommended dose of isoniazid (INH) for intermittent therapy under the RNTCP is 8-12 mg/kg body weight and by the World Health Organization (WHO) for daily therapy is 10-15 mg/kg body weight.

Aims: To evaluate the blood levels and pharmacokinetics of INH, in children suffering from tuberculosis, at doses administered under the weight band system of the Revised National Tuberculosis Control Program (RNTCP) 2009 of India.

Design: Prospective, open label, non-randomized single-dose study conducted in 20 children in the age group 5-12 years attending the outpatient, chest clinic of a tertiary care hospital.

Results: Group I (n = 8) included children who received INH in a dose of 10 mg/kg body weight or more and Group II (n = 12) included those who received INH in a dose less than 10 mg/kg body weight. The mean peak INH concentration (Cmax) was 6.03 ± 1.4 μg/mL and this was achieved in 2 hours (Tmax). The mean serum INH concentration was significantly higher in children who received INH in dose more than 10 mg/kg (Group I) as compared to those who received INH in doses lesser than 10 mg/kg body weight (Group II) at all-time points except at 2 hours (P < 0.05). The Cmax was also lower in Group II patients in comparison to Group I patients. Area under the concentration time curve (AUC) was significantly lower in Group II patients (P value 0.002). The elimination half-life of INH was 4.3 ± 0.4 h, elimination rate constant 0.16 ± 0.01/h, the volume of distribution 44.05 ± 5.3 L and clearance 7.1 ± 0.8 L/h.

Conclusions: Lower blood levels and AUC of INH were achieved in children receiving doses of INH lesser than 10 mg/kg body weight. Long elimination half-life of INH is indicative of a slower rate of metabolism. Lower INH levels despite a slower rate of drug metabolism indicate caution with the INH doses being administered to children for intermittent therapy under the RNTCP.

Keywords: Children; India; Isoniazid; Pharmacokinetics; Tuberculosis.