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Pharmacokinetics of pyrazinamide in children suffering from pulmonary tuberculosis
1Department of Pharmacology, Maulana Azad Medical College and Associated Hospitals, New Delhi, India.
Insights
Pyrazinamide, an anti-tuberculosis drug, maintained therapeutic levels for over 6 hours in children with pulmonary tuberculosis. Pediatric patients showed slower absorption and longer half-life compared to adults.
Area of Science:
- Pharmacology
- Clinical Pharmacology
- Microbiology
Background:
- Tuberculosis remains a significant global health challenge, necessitating effective treatment strategies.
- Pyrazinamide is a crucial first-line anti-tuberculosis drug, particularly effective against Mycobacterium tuberculosis in acidic environments.
- Understanding the pharmacokinetics of pyrazinamide in pediatric populations is essential for optimizing treatment efficacy and safety.
Purpose of the Study:
- To evaluate the pharmacokinetics of pyrazinamide in children aged 6 to 12 years diagnosed with pulmonary tuberculosis.
- To determine if achieved serum concentrations of pyrazinamide remain above the minimum inhibitory concentration (MIC) for Mycobacterium tuberculosis.
Main Methods:
- A cohort of 10 pediatric patients with pulmonary tuberculosis received pyrazinamide at a dose of 35 mg/kg.
- Serial blood samples were collected over 24 hours post-administration.
- Serum pyrazinamide concentrations were quantified using spectrophotometry.
Main Results:
- Serum pyrazinamide levels exceeded the MIC of 20 µg/ml for Mycobacterium tuberculosis for at least 6 hours in all patients, and up to 12 hours in 60% of patients.
- The mean peak serum concentration (Cmax) was 41.2 ± 11.8 µg/ml, achieved at 2.9 ± 1.7 hours (Tmax).
- Key pharmacokinetic parameters included an elimination half-life of 10.9 ± 4.5 hours, volume of distribution of 16.1 ± 10.9 L, and clearance of 20.2 ± 16.3 ml/minute.
Conclusions:
- A pyrazinamide dose of 35 mg/kg ensures therapeutic concentrations above the MIC for Mycobacterium tuberculosis for over 6 hours in pediatric patients.
- Pediatric patients appear to exhibit slower absorption, reduced clearance, a longer elimination half-life, and a larger volume of distribution for pyrazinamide compared to adults.
- These findings suggest potential dose adjustments or therapeutic drug monitoring may be beneficial in pediatric tuberculosis treatment.
Setting:
The Paediatric and Clinical Pharmacology unit of Maulana Azad Medical College and Associated Lok Nayak Hospital, New Delhi, India.
Objective:
The pharmacokinetics of the anti-tuberculosis drug pyrazinamide was evaluated in 10 children aged 6 to 12 years suffering from pulmonary tuberculosis.
Methods:
Serial blood samples were collected at 0, 1, 2, 4, 6, 12 and 24 hours after administration of pyrazinamide in a dose of 35 mg/kg. Serum pyrazinamide levels were analysed by spectrophotometry.
Results:
The serum concentrations of pyrazinamide were above the minimum inhibitory concentration of 20 microg/ml of pyrazinamide for Mycobacterium tuberculosis up to 6 hours after drug administration in all the patients, and up to 12 hours in six patients. The mean peak serum concentration of pyrazinamide was 41.2+/-11.8 microg/ml, and this was attained in (Tmax) 2.9+/-1.7 hours. The elimination half life was 10.9+/-4.5 hours, the volume of distribution 16.1+/-10.9 litres and clearance 20.2+/-16.3 ml/minute. The corresponding mean residence time was 19.9+/-14.6 hours.
Conclusion:
The serum pyrazinamide concentrations achieved with a dose of 35 mg/kg were above the minimum inhibitory concentration of pyrazinamide for M. tuberculosis for over 6 hours after drug administration. It appears that the absorption and the clearance of pyrazinamide is slower, the elimination half life longer and the volume of distribution higher in children compared with the reported values in the adult population.