Hepatic Drug Metabolism in Pediatric Patients

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For many drugs, clearance is the primary factor driving dosing regimens. In young children, hepatic metabolic clearance is influenced by maturational changes in the expression and activity of drug-metabolizing enzymes, as well as by changes in hepatic blood flow and perfusion, plasma protein binding, and active transport processes. The largest maturational changes in the different determinants of hepatic metabolic clearance are observed in the first months and years of life with largest interindividual variability in the youngest age ranges. Together, the physiochemical properties of a given drug and the interplay of the aforementioned factors in a developmental context determine the drug's total hepatic clearance. Knowledge on the maturational processes influencing hepatic drug clearance is limited. Centrally, an understanding of the ontogeny of drug-metabolizing enzymes is critical for sound clinical judgment regarding the use of certain drugs in young children.

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