Related Experiment Videos
INH and streptomycin in Ethiopian children with tuberculosis and different nutritional status
1Departments of Pediatrics, St. Göran's Hospital, Stockholm, Sweden.
Insights
Tuberculosis treatment with isoniazid (INH) and streptomycin was effective in Ethiopian children, regardless of nutritional status. While INH showed slow acetylation, streptomycin absorption was good, though kwashiorkor impacted its excretion.
Area of Science:
- Pharmacokinetics and Pharmacodynamics
- Pediatric Infectious Diseases
- Nutritional Biochemistry
Background:
- Tuberculosis (TB) remains a significant global health challenge, particularly in resource-limited settings.
- Nutritional status can influence drug absorption, distribution, metabolism, and excretion (ADME) in children.
- Understanding the pharmacokinetics of first-line anti-TB drugs like isoniazid (INH) and streptomycin is crucial for optimizing treatment efficacy in diverse pediatric populations.
Purpose of the Study:
- To evaluate the plasma concentrations and pharmacokinetic profiles of isoniazid (INH) and streptomycin in Ethiopian children with tuberculosis.
- To assess the impact of different nutritional statuses (normal, underweight, marasmus, kwashiorkor) on INH and streptomycin pharmacokinetics.
- To determine the therapeutic efficacy and safety of standard INH and streptomycin doses in this pediatric cohort.
Main Methods:
- Plasma concentrations of INH and streptomycin were measured in 45 Ethiopian children diagnosed with tuberculosis.
- Children were categorized into nutritional groups: normal, underweight, marasmus, and kwashiorkor.
- Pharmacokinetic parameters, including terminal half-life (t1/2), were calculated for both drugs.
Main Results:
- Isoniazid (INH) was well absorbed across all nutritional groups, achieving therapeutic plasma levels.
- A significant proportion of children exhibited a slow acetylation of INH (t1/2 ≥ 2 hours).
- Streptomycin demonstrated good absorption, reaching therapeutic levels with 20 mg/kg intramuscularly; however, kwashiorkor was associated with increased streptomycin t1/2, suggesting reduced renal excretion.
Conclusions:
- Standard doses of isoniazid and streptomycin are pharmacokinetically suitable for treating tuberculosis in Ethiopian children, even with varying nutritional statuses.
- Slow isoniazid acetylation is common in this population, necessitating consideration in treatment regimens.
- Kwashiorkor may impair streptomycin renal excretion, potentially requiring dose adjustments or closer monitoring.
Abstract:
The plasma concentration of INH and streptomycin was followed in 45 Ethiopian children with tuberculosis. The children were grouped according to their nutritional status as normal, underweight, marasm and kwashiorkor. INH was well absorbed in all nutritional groups to give therapeutically active plasma levels. When terminal half life (t1/2) of INH was calculated for individual patients there were more children in all nutritional groups with t1/2 greater than or equal to 2 hours than less than 2 hours, indicating a slow acetylation of INH. Streptomycin was well absorbed in all nutritional groups and therapeutic levels were obtained with 20 mg/kg i.m. After 30 mg/kg i.m. of streptomycin kwashiorkor children had an increased t1/2 of streptomycin indicating a decreased renal excretion of the drug in kwashiorkor. The clinical follow-up of the children indicated that serious tuberculosis could be successfully treated with INH and streptomycin in the doses used.