Age-related differences in hepatic drug clearance in children: studies with lorazepam and antipyrine.
The disposition of intravenous antipyrine and lorazepam, administered as model substrates for hepatic oxidative metabolism and conjugation, was evaluated in 50 children (mean age, 7.8 years; range, 2.3 to 17.8 years) with acute lymphocytic leukemia in complete remission and compared with a group of ten healthy adults. Antipyrine clearance normalized to body weight was significantly greater in children than in adults (0.91 versus 0.59 ml/min/kg; p = 0.012), but was not different when normalized to body surface area. In contrast, lorazepam total clearance (CL) and unbound clearance (CLu) normalized to body weight were not significantly different between children and adults but were smaller in children when normalized to body surface area (CL = 31.9 versus 40.6 ml/min/m2, p = 0.036; CLu = 352 versus 485 ml/min/m2, p = 0.010). The mean lorazepam fraction unbound in children was 0.087, which was not different from adult volunteers (0.084). This study has identified significant differences between children and adults in the disposition of these two compounds, with higher milliliter per minute per kilogram clearance for antipyrine but not lorazepam.
Crom
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WR
Pharmacokinetics and Pharmacodynamics Section, St. Jude Children's Research Hospital, Memphis, TN 38105.
Relling
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MV
Christensen
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ML
Rivera
G K
GK
Evans
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WE
D000293:Adolescent; D000328:Adult; D000367:Age Factors; D000983:Antipyrine / Q000008:administration & dosage / Q000493:pharmacokinetics*; D001835:Body Weight; D002648:Child; D002675:Child, Preschool; D005260:Female; D006801:Humans; D007275:Injections, Intravenous; D008099:Liver / Q000378:metabolism*; D008140:Lorazepam / Q000008:administration & dosage / Q000493:pharmacokinetics*; D008297:Male; D008657:Metabolic Clearance Rate; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000378:metabolism
D008140:Lorazepam; D000983:Antipyrine