Blood levels of pyrazinamide in children at doses administered under the Revised National Tuberculosis Control Program.
OBJECTIVE
To evaluate the blood levels, pharma-cokinetics and pharmacodynamic indices of pyrazinamide (PZA) in children suffering from tuberculosis, at doses administered under the weight band system of Revised National Tuberculosis Control Program of India (RNTCP) of India.


METHODS
Prospective, open-label, non-randomized single-dose study.


METHODS
20 children in the age group 5-12 years attending out-patient tuberculosis clinic of a tertiary hospital.


METHODS
Blood levels of pyrazinamide after single dose administration, as per the weight band system of RNTCP.


RESULTS
Group I (n=7) included children who received pyrazinamide within the recommended 30-35 mg/kg dose (mean 31.9 ± 0.8 mg/kg) and Group II (n=13) included those who received a dose lower than 30 -35 mg/kg (mean 28.1 ± 0.3 mg/kg). The Cmax (95% CI of difference 2.2, 13.2; P=0.008) and AUC (95% CI of difference 28.6, 208.1; P=0.01) were significantly lower in Group II. The duration of time for which the concentration was maintained above 25 ug ml-1 was 4-8 h in Group I and 3-5.5 h in Group II (95% CI of difference 0.1, 2.0; P=0.03). The half life, elimination rate constant, clearance and volume of distribution were comparable in the two groups. The ratios of Cmax and AUC to MIC (25 ug ml-1) in children were lower than that recommended for PZA in adults.


CONCLUSIONS
Lower blood concentrations are being attained in children receiving PZA doses under the existing weight band system of RNTCP of India. The weight bands may need to be revised and dose recommendations be based on pharmacokinetic and efficacy data in children.
Department of Pharmacology, Maulana Azad Medical College and Associated Hospitals, Bahadurshah Zafar Marg, New Delhi 110 002, India. roy.vandana@gmail.com
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Roy
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Sahni
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Gupta
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Sethi
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Khanna
D000995:Antitubercular Agents / Q000008:administration & dosage* / Q000097:blood* / Q000493:pharmacokinetics; D001835:Body Weight; D002648:Child; D002675:Child, Preschool; D003140:Communicable Disease Control; D006801:Humans; D007194:India; D011446:Prospective Studies; D011718:Pyrazinamide / Q000008:administration & dosage* / Q000097:blood* / Q000493:pharmacokinetics; D014376:Tuberculosis / Q000097:blood* / Q000188:drug therapy* / Q000378:metabolism
D000995:Antitubercular Agents; D011718:Pyrazinamide