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Pharmacokinetic study of antipyrine in malnourished children
Insights
Children with protein calorie malnutrition exhibit altered drug metabolism, showing a longer antipyrine plasma half-life and reduced clearance. Nutritional rehabilitation restored these metabolic functions to normal levels.
Area of Science:
- Pediatric Nutrition
- Pharmacokinetics
- Biochemistry
Background:
- Protein calorie malnutrition (PCM) significantly impacts physiological functions, including drug metabolism.
- Microsomal oxidative enzyme activity in the liver is crucial for drug clearance.
- Altered drug metabolism in malnourished children can affect therapeutic efficacy and safety.
Purpose of the Study:
- To investigate the impact of protein calorie malnutrition on the plasma half-life and metabolic clearance rate of antipyrine in children.
- To assess the reversibility of altered drug metabolism following nutritional rehabilitation.
Main Methods:
- Intravenous administration of antipyrine (16 mg/kg) to 10 malnourished children and 5 healthy controls.
- Measurement of plasma antipyrine half-life and metabolic clearance rate.
- Restudy of 5 malnourished children after 17-25 days of nutritional rehabilitation.
Main Results:
- Malnourished children showed a significantly increased plasma half-life (10.4 hr vs. 6.3 hr) and decreased metabolic clearance rate (47.1 ml/hr/kg vs. 70.1 ml/hr/kg) of antipyrine compared to controls.
- These changes suggest reduced hepatic microsomal oxidative enzyme activity in malnourished children.
- After nutritional rehabilitation, antipyrine half-life decreased (6.6 hr) and clearance increased (66.5 ml/hr/kg), approaching normal values.
Conclusions:
- Protein calorie malnutrition impairs antipyrine metabolism in children, indicating reduced liver enzyme function.
- Nutritional rehabilitation effectively reverses these metabolic derangements.
- Drug therapy regimens for children with PCM may require adjustments due to altered pharmacokinetics.
Abstract:
Plasma half-life and metabolic clearance rate of antipyrine administered intravenously in a dose of 16 mg/kg body weight was studied in 10 children suffering from protein calorie malnutrition and five normal children matched in age and sex. Plasma half-life was increased and metabolic clearance rate was decreased in malnourished children (10.4 hr and 47.1 ml/hr per kg, respectively) in comparison to controls (6.3 hr and 70.1 ml/hr per kg, respectively). This observation indirectly reflects the lowered activity of microsomal oxidative enzyme of liver. Five children were restudied after nutritional rehabilitation of 17 to 25 days. Antipyrine plasma half-life decreased to 6.6 hr and metabolic clearance rate increased to 66.5 ml/hr per kg. These values were similar to those in normal children indicating biological recovery. The drug therapy in children with protein calorie malnutrition requires reconsideration in light of these observations.