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Malnutrition and drugs: clinical implications.
1Pediatric Gastroenterology, Postgraduate Institute of Medical Education and Research, Chandigarh, India.
Developmental Pharmacology and Therapeutics
|January 1, 1990
Summary
Malnourished children exhibit altered drug elimination, with slower clearance and increased toxicity risks for medications like isoniazid and rifampicin. Dosing adjustments are crucial for effective and safe treatment in these vulnerable populations.
Area of Science:
- Pharmacology
- Pediatrics
- Nutritional Science
Background:
- Malnutrition significantly impacts physiological functions, including drug metabolism and elimination.
- Altered drug pharmacokinetics in malnourished children can lead to therapeutic failure or toxicity.
Purpose of the Study:
- To investigate the impact of malnutrition on the elimination kinetics of various drugs in children.
- To assess drug biotransformation and potential toxicity in malnourished pediatric populations.
Main Methods:
- Timed plasma concentration curves were used to determine elimination kinetics for chloramphenicol, antipyrine, acetaminophen, and sulphadiazine.
- Urinary metabolite excretion and hepatic enzyme activity (aminopyrine demethylase, chloramphenicol glucuronyl transferase) were analyzed.
- Drug levels and hepatotoxicity were monitored in children receiving therapeutic drugs.
Main Results:
- Malnourished children showed increased plasma half-life and reduced elimination rate constants for studied drugs.
- Area under the curve (AUC) was elevated, indicating slower drug clearance.
- Decreased urinary excretion of drug metabolites and diminished hepatic enzyme activity suggested impaired biotransformation.
- Higher steady-state drug levels and a 3-fold increase in hepatotoxicity with isoniazid and rifampicin were observed in malnourished children.
Conclusions:
- Liver metabolism and drug elimination are significantly impaired in malnourished children.
- Therapeutic drug monitoring and dose modification are essential to prevent toxicity and ensure efficacy.
- Malnutrition increases the risk of hepatotoxicity from antitubercular therapy, irrespective of acetylator status.
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