Malnutrition and pharmacokinetics of penicillin in Ethiopian children
P Bolme1, M Eriksson, L Paalzow
1Ethio-Swedish Children's Hospital, Addis Ababa, Ethiopia.
Insights
Malnourished children show reduced penicillin clearance, impacting oral bioavailability. Oral penicillin doses should be increased for fasting, severely ill children to ensure effective treatment.
Area of Science:
- Pharmacokinetics
- Pediatrics
- Nutritional Science
Background:
- Nutritional status significantly influences drug metabolism and efficacy.
- Penicillin is a critical antibiotic for pediatric infections.
- Understanding drug pharmacokinetics in malnutrition is vital for treatment optimization.
Purpose of the Study:
- To investigate the effect of nutritional status on penicillin pharmacokinetics in children.
- To compare penicillin plasma concentrations across different nutritional groups (normal, underweight, marasmus, kwashiorkor).
- To evaluate the impact of administration route and fasting state on penicillin bioavailability.
Main Methods:
- Administered penicillin intravenously, intramuscularly, or orally to 104 children with varying nutritional status.
- Monitored plasma penicillin concentrations at regular intervals post-administration.
- Analyzed pharmacokinetic parameters including plasma clearance, half-life, and volume of distribution.
Main Results:
- Significantly decreased plasma clearance of penicillin observed in all malnourished groups compared to normal weight-for-age children.
- Penicillin half-life remained unchanged across nutritional groups due to a decreased volume of distribution in malnourished children.
- Oral penicillin bioavailability was reduced in non-fasting individuals, with the most pronounced effect in children with marasmus and kwashiorkor.
Conclusions:
- Nutritional status significantly alters penicillin pharmacokinetics, primarily affecting plasma clearance and bioavailability.
- Oral penicillin administration in severely malnourished children requires dose adjustment and should ideally occur during fasting.
- Optimized dosing strategies are crucial for effective penicillin therapy in undernourished pediatric populations.
Abstract:
Penicillin was given to 104 children with different nutritional status, normal, underweight, marasmus and kwashiorkor. Penicillin was given either intravenously, intramuscularly or orally and the plasma concentration was followed at regular times after administration. There was a significantly decreased plasma clearance of penicillin in all malnourished groups compared to the normal weight-for-age group. The half-lives of penicillin were, however, not significantly different between the nutritional groups. This was explained by the fact that also the volume of distribution was decreased in the malnourished group with a net result that the half-life was unchanged. The bioavailability was decreased if penicillin was given to non-fasting individuals. The greatest difference between fasting and non-fasting was seen in the severely malnourished children with marasmus and kwashiorkor. Therefore, it is advised that, if penicillin is given orally to very sick and undernourished children, the dose should be increased and preferably be given in the fasting state.
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