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Control of streptomycin and isoniazid in malnourished children treated for tuberculosis
Insights
Malnourished children treated for tuberculosis showed adequate absorption of oral isoniazid. However, streptomycin dosing requires caution to prevent toxicity, with renal function remaining unaffected.
Area of Science:
- Pharmacology
- Pediatrics
- Infectious Diseases
Background:
- Tuberculosis treatment in malnourished children presents pharmacokinetic challenges.
- Understanding drug absorption and clearance is crucial for optimizing therapeutic outcomes.
- Malnutrition may alter drug metabolism and excretion, necessitating careful dosage adjustments.
Purpose of the Study:
- To evaluate plasma levels of streptomycin and isoniazid in malnourished children undergoing tuberculosis treatment.
- To assess the impact of malnutrition on the pharmacokinetics of these essential anti-tuberculosis drugs.
- To provide dosing recommendations for streptomycin and evaluate isoniazid absorption in this vulnerable population.
Main Methods:
- Plasma concentrations of streptomycin and isoniazid were measured in 12 malnourished children.
- Streptomycin was administered intramuscularly (25-50 mg/kg/24 hours).
- Isoniazid was administered orally (10 mg/kg/24 hours).
Main Results:
- High initial plasma levels of streptomycin were observed, with an estimated half-life of 3.5 hours.
- Streptomycin clearance was not significantly affected by malnutrition, suggesting preserved renal function.
- Oral isoniazid was effectively absorbed, with measurable plasma levels achieved in all participants, indicating rapid inactivation in most.
Conclusions:
- Streptomycin dosage should not exceed 25 mg/kg/24 hours in malnourished children to avoid potential toxicity, especially without therapeutic drug monitoring.
- Malnourished children can effectively absorb oral isoniazid, but rapid inactivation is common.
- These findings support optimized anti-tuberculosis drug regimens for pediatric populations with malnutrition.
Abstract:
In 12 malnourished children, who were treated for tuberculosis, plasma levels of streptomycin and isoniazid were followed. Streptomycin was administered i.m. in a dose of 25-50 mg/kg/24 hours. High initial plasma levels were reached (mean: 44.3 mug/ml at 30 min). Streptomycin levels were followed for 5 hours and the mean plasma level at that time was 17.0 mug/ml. From the present data a plasma half life of streptomycin of 3.5 hours has been estimated. It is advised that streptomycin should not be given in doses above 25 mg/kg/24 hours to avoid potential toxic plasma levels especially if plasma levels cannot be measured. It is also concluded from our study that renal function is not affected in malnourished children to an extent where streptomycin clearance is greatly affected. Isoniazid was given orally, 10 mg/kg/24 hours. From 30 min to 6 hours after administration, mean plasma levels of isoniazid above 0.5 mug/ml were observed. In all children measurable plasma levels were obtained. It is concluded that also children with malnutrition can absorb isoniazid after oral administration. From our data it is suggested that the majority of the children in our study were rapid inactivators of isoniazid.