Disposition of antineoplastic agents in the very young child.
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)
McLeod
H L
HL
St Jude Children's Research Hospital, Pharmaceutical Division, Memphis, TN 38101.
Relling
M V
MV
Crom
W R
WR
Silverstein
K
K
Groom
S
S
Rodman
J H
JH
Rivera
G K
GK
Crist
W M
WM
Evans
W E
WE
D000367:Age Factors; D000970:Antineoplastic Agents / Q000493:pharmacokinetics* / Q000627:therapeutic use / Q000633:toxicity; D001798:Blood Proteins / Q000378:metabolism; D002648:Child; D002675:Child, Preschool; D004317:Doxorubicin / Q000493:pharmacokinetics; D005047:Etoposide / Q000493:pharmacokinetics; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D008099:Liver / Q000187:drug effects / Q000473:pathology; D015122:Mercaptopurine / Q000493:pharmacokinetics; D008727:Methotrexate / Q000493:pharmacokinetics; D009369:Neoplasms / Q000097:blood / Q000188:drug therapy*; D009420:Nervous System / Q000187:drug effects / Q000473:pathology; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000188:drug therapy; D013713:Teniposide / Q000493:pharmacokinetics
D000970:Antineoplastic Agents; D001798:Blood Proteins; D005047:Etoposide; D004317:Doxorubicin; D013713:Teniposide; D015122:Mercaptopurine; D008727:Methotrexate