Pharmacokinetics in the newborn.
In addition to differences in the pharmacodynamic response in the infant, the dose and the pharmacokinetic processes acting upon that dose principally determine the efficacy and/or safety of a therapeutic or inadvertent exposure. At a given dose, significant differences in therapeutic efficacy and toxicant susceptibility exist between the newborn and adult. Immature pharmacokinetic processes in the newborn predominantly explain such differences. With infant development, the physiological and biochemical processes that govern absorption, distribution, metabolism, and excretion undergo significant growth and maturational changes. Therefore, any assessment of the safety associated with an exposure must consider the impact of these maturational changes on drug pharmacokinetics and response in the developing infant. This paper reviews the current data concerning the growth and maturation of the physiological and biochemical factors governing absorption, distribution, metabolism, and excretion. The review also provides some insight into how these developmental changes alter the efficiency of pharmacokinetics in the infant. Such information may help clarify why dynamic changes in therapeutic efficacy and toxicant susceptibility occur through infancy.
Alcorn
Jane
J
College of Pharmacy and Nutrition, University of Saskatchewan, 110 Science Place, SK, S7N 5C9, Saskatoon, Canada. jane.alcorn@usask.ca
McNamara
Patrick J
PJ
D005753:Gastric Mucosa / Q000378:metabolism; D006801:Humans; D007231:Infant, Newborn; D007408:Intestinal Absorption; D007668:Kidney / Q000378:metabolism; D008099:Liver / Q000378:metabolism; D004364:Pharmaceutical Preparations / Q000378:metabolism*; D010599:Pharmacokinetics; D014018:Tissue Distribution
D004364:Pharmaceutical Preparations