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Absorption of intramuscular phenobarbitone in children with severe falciparum malaria
F Kuile1, F Nosten, T Chongsuphajaisiddhi
1Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand.
Insights
Intramuscular phenobarbitone is well absorbed in children with severe falciparum malaria. While generally safe, it may increase drowsiness and coma depth in the short term.
Area of Science:
- Pharmacology
- Pediatrics
- Infectious Diseases
Background:
- Severe falciparum malaria poses significant risks in children, including neurological complications.
- Anticonvulsant therapy is crucial for managing malaria-associated seizures.
- Phenobarbitone is a commonly used anticonvulsant with established absorption profiles.
Purpose of the Study:
- To evaluate the absorption of intramuscular phenobarbitone in children with severe falciparum malaria.
- To compare clinical outcomes between phenobarbitone recipients and a placebo group.
- To assess the safety and tolerability of phenobarbitone in this patient population.
Main Methods:
- A study involving 11 Karen children (1.7-11 years) with severe falciparum malaria receiving intramuscular phenobarbitone (7 mg.kg-1).
- Comparison with 9 children receiving an identical placebo.
- Clinical observations and phenobarbitone plasma concentrations were monitored.
Main Results:
- Phenobarbitone was rapidly absorbed, achieving peak concentrations comparable to previous studies.
- No observable toxicity was noted, but phenobarbitone recipients showed increased somnolence and deepened coma.
- No post-treatment convulsions occurred, though the study size precluded efficacy assessment.
Conclusions:
- Intramuscular phenobarbitone demonstrates good absorption in children with severe malaria.
- Further research is needed to determine the optimal prophylactic anticonvulsant dose.
- Potential for increased sedation warrants careful monitoring post-administration.
Abstract:
The absorption of intramuscular phenobarbitone 7 mg.kg-1 was studied in 11 Karen children aged between 1.7 and 11 y with severe falciparum malaria. Eight of the children were comatose. Clinical findings were compared with those in 9 further children with severe malaria of similar age range (four of whom were unconscious), who received an identical placebo. One child, who had received placebo, had repeated convulsions and died 1 h after admission to hospital. The remainder made an uncomplicated recovery. There were no convulsions subsequent to treatment, although the study was too small to assess anticonvulsant efficacy. There was no observable toxicity, but phenobarbitone recipients had a significant tendency to deepen in their level of coma or to become sleepy within the 4 h after drug administration. Phenobarbitone was rapidly absorbed, reaching a mean (range) peak concentration of 34.2 [29.3-42.6] mumol.l-1 in a median (range) of 4 (2.5-12) h. These values are comparable to those previously reported in healthy children and in children with febrile convulsions. Intramuscular phenobarbitone is well absorbed in children with severe malaria; the optimum prophylactic anticonvulsant dose remains to be determined.