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Disposition of acetaminophen in children with protein calorie malnutrition
Insights
Children with Protein Calorie Malnutrition (PCM) show significantly slower acetaminophen elimination, increasing drug half-life and exposure. Rehabilitation improved these pharmacokinetic parameters, suggesting revised drug dosing is necessary for malnourished children.
Area of Science:
- Pharmacokinetics
- Pediatric Nutrition
- Drug Metabolism
Background:
- Protein Calorie Malnutrition (PCM) can alter drug metabolism and disposition.
- Acetaminophen is a commonly used analgesic and antipyretic in children.
- Understanding drug pharmacokinetics in malnourished children is crucial for safe and effective therapy.
Purpose of the Study:
- To investigate the disposition of acetaminophen in children with PCM.
- To compare acetaminophen pharmacokinetic parameters between PCM children and healthy controls.
- To assess the impact of nutritional rehabilitation on acetaminophen disposition.
Main Methods:
- Studied acetaminophen disposition in 11 PCM children and 5 age-matched controls.
- Administered a single oral dose of 10 mg/kg acetaminophen.
- Analyzed plasma concentration-time curves to determine pharmacokinetic parameters (Ka, Ke, t1/2, AUC).
Main Results:
- Acetaminophen absorption rate constant (Ka) was unchanged in PCM children.
- Elimination rate constant (Ke) was significantly decreased in PCM children (0.108 h-1 vs. 0.170 h-1).
- Plasma half-life (t1/2) and Area Under the Curve (AUC) were significantly increased in PCM children, indicating prolonged drug exposure.
Conclusions:
- PCM significantly impairs acetaminophen elimination, leading to longer drug half-life and increased systemic exposure.
- Nutritional rehabilitation in PCM children led to the normalization of acetaminophen elimination parameters.
- Acetaminophen dosing regimens may require adjustment in children with PCM to prevent potential toxicity.
Abstract:
Acetaminophen disposition was studied in 11 children suffering from Protein Calorie Malnutrition (PCM) and 5 (age matched) control subjects using the time plasma concentration curve obtained after a single oral administration of 10 mg/kg of the drug. Absorption rate constant (Ka) was not altered in PCM. Elimination rate constant (Ke) was decreased significantly. PCM children had Ke 0.108 +/- 0.015 h-1 in comparison to the control value of 0.170 +/- 0.022 h-1. Plasma half-life (t1/2) was increased in PCM (8.14 +/- 1.30 h) in comparison of the control (4.33 +/- 0.52 h). Area under the curve (AUC) was also significantly increased in PCM (88.88 +/- 21.36 ug h/ml/kg) compared to the control (25.05 +/- 2.99 ug h/ml/kg). Time of drug disappearance was 44.7 +/- 7.1 hours in PCM compared to 24.6 +/- 3.3 hours in the control. Five PCM subjects could be restudied after rehabilitation and they demonstrated the return of elimination parameters towards control values. Drug therapy needs revision in light of these findings.