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Age‐related differences in hepatic drug clearance in children: Studies with lorazepam and antipyrine
Author(s) -
Crom William R,
Relling Mary V,
Christensen Michael L,
Rivera Gaston K,
Evans William E
Publication year - 1991
Publication title -
clinical pharmacology and therapeutics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.941
H-Index - 188
eISSN - 1532-6535
pISSN - 0009-9236
DOI - 10.1038/clpt.1991.117
Subject(s) - lorazepam , pharmacokinetics , body surface area , disposition , liter , body weight , medicine , chemistry , anesthesia , psychology , social psychology
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 (CL u ) 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/m 2 , p = 0.036; CL u = 352 versus 485 ml/min/m 2 , 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. Clinical Pharmacology and Therapeutics (1991) 50, 132–140; doi: 10.1038/clpt.1991.117