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Disposition of antineoplastic agents in the very young child
H L McLeod1, M V Relling, W R Crom
1St Jude Children's Research Hospital, Pharmaceutical Division, Memphis, TN 38101.
Insights
Pediatric cancer drug pharmacokinetics show age-related differences. Methotrexate clearance was lower in infants, while etoposide clearance varied by weight normalization in young children.
Area of Science:
- Pharmacology
- Pediatric Oncology
- Drug Metabolism
Background:
- Physiologic maturation significantly alters drug pharmacokinetics in children.
- Limited pharmacokinetic data exist for anticancer drugs in young children.
Purpose of the Study:
- To compare pharmacokinetic data of anticancer agents in infants (<1 year) versus older children (>1 year).
- To identify age-related differences in drug disposition for pediatric cancer patients.
Main Methods:
- Retrospective analysis of pharmacokinetic data for six anticancer agents.
- Comparison of drug clearance and half-life between infants and children.
- Normalization of clearance by body surface area and body weight.
Main Results:
- Methotrexate clearance was significantly lower in infants (0.26-0.99 years) compared to children (1-19 years).
- Etoposide clearance was significantly lower in infants (0.5-1 year) when normalized to body weight.
- No significant differences were observed for teniposide and cytarabine clearance, or etoposide clearance normalized to body surface area.
Conclusions:
- Infants exhibit distinct pharmacokinetic profiles for certain anticancer drugs compared to older children.
- Age-related differences in drug disposition necessitate careful dosing in pediatric cancer patients.
- Further research is needed for very young infants (<2 months) due to data limitations.
Abstract:
Maturation of physiologic process which govern the disposition of pharmacologic agents can yield significant changes in absorption, distribution, metabolism, and elimination of drugs in neonates, infants and children. However, there are very little data concerning the disposition of anticancer drugs in young children. Pharmacokinetic data for six anticancer agents were compared in infants less than 1 year of age and children greater than 1 year of age treated at St Jude Children's Research Hospital. No pharmacokinetic data were available for infants less than 2 months of age. Median methotrexate clearance tended to be lower in four infants (0.26-0.99 years) vs 108 children (1-19 years): 80 vs 103 ml min-1 m-2, respectively (P = 0.01). There was no difference in the median 42 h methotrexate concentration. Teniposide systemic clearance and terminal half-life and cytarabine systemic clearance were not different between the two groups. There was no significant difference in etoposide systemic clearance when normalised to body surface area (ml min-1 m-2), however a significantly lower systemic clearance relative to body weight (ml min-1 kg-1) was observed in two infants, 0.5 to 1 year of age, vs 23 children, 3-18 years of age. Doxorubicin systemic clearance was not significantly different between the two groups when systemic clearance was expressed in ml min-1 kg-1. However, there was a trend toward a lower rate of systemic clearance in ml min-1 m-2 in infants.(ABSTRACT TRUNCATED AT 250 WORDS)