Drug disposition and the dynamics of drug responsiveness change with maturation and aging. Such changes tend to occur in an orderly sequence at predictable stages in life, but their onset and extent can vary widely from one person to another. During infancy and childhood, these changes are usually rapid and are either periodic or cyclic, whereas they tend to occur more gradually but asynchronously with advancing age so that individual variability in disposition and response increases substantially among elderly persons. In general, bodily clearance of therapeutic agents and toxicants is an age-related function of metabolic and renal capacity. During infancy, transitory insufficiency in metabolic pathways explains the reduced metabolism of most drugs, while maturation of existing renal structures accounts for the low level of drug clearance. Consequently, the dose and/or time of administration of most drugs is decreased during the first few weeks after birth to avoid toxicity. In elderly persons, a reduction in hepatic and renal clearance prolongs drug elimination, and pharmacodynamic changes may alter the sensitivity to many drugs that are frequently used in older persons. However, broad generalizations are difficult, and less information of a more limited character is available because pharmacodynamic variation depends on the specific drug under consideration.
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