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Pharmacokinetics of amphotericin B in infants and children
Insights
Pharmacokinetics of amphotericin B (AmB) in children differ from adults, with lower serum levels and faster elimination. These findings are crucial for optimizing pediatric dosing regimens for fungal infections.
Area of Science:
- Pediatric Pharmacology
- Mycology
- Infectious Diseases
Background:
- Limited pharmacokinetic data exists for amphotericin B (AmB) in pediatric populations.
- Understanding AmB's behavior in children is essential for effective treatment of invasive fungal infections.
Purpose of the Study:
- To evaluate the pharmacokinetics of amphotericin B (AmB) in infants and children.
- To compare pediatric AmB pharmacokinetics with existing adult data.
Main Methods:
- A pharmacokinetic study involving ten pediatric patients (five premature infants, five older children).
- Patients received AmB doses ranging from 0.25-1.0 mg/kg/24 hr for Candida infections.
- Serum AmB concentrations were measured by bioassay to determine pharmacokinetic parameters using a one-compartment model.
Main Results:
- Pediatric patients exhibited a smaller volume of distribution and more rapid elimination clearance compared to adults.
- Mean serum AmB concentrations were approximately half those observed in adults at comparable doses.
- Significant interpatient variability in AmB levels was noted, particularly in premature infants.
Conclusions:
- Amphotericin B pharmacokinetics in infants and children significantly differ from adult profiles.
- These pharmacokinetic differences necessitate careful consideration for establishing optimal pediatric dosing strategies.
- Further research is warranted to refine AmB dosing for improved pediatric outcomes in fungal infections.
Abstract:
The pharmacokinetics of amphotericin B (AmB) have not previously been evaluated in children. Five very small, premature infants and five older children received 0.25-1.0 mg of AmB/kg per 24 hr for Candida infections. Serum concentrations of AmB, measured by bioassay, were used to determine various pharmacokinetic parameters of AmB. A one-compartment model of drug distribution was most consistent with the data. The volume of AmB distributed per kilogram of body weight was smaller and the elimination clearance more rapid than those previously reported for adults. Serum levels were approximately one-half those seen in adults given comparable doses. The mean concentrations of AmB after various doses were as follows: at 0.25 mg/kg, 0.08 microgram/ml; at 0.50 mg/kg, 0.20 microgram/ml; at 0.75 mg/kg, 0.42 microgram/ml; and at 1.0 mg/kg, 0.54 microgram/ml. Interpatient variability was, however, marked, especially among the premature infants. AmB pharmacokinetics are different in infants and children than in adults; these differences may have implications for determining optimal pediatric dosing regimens.