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Review
. 2014 Oct-Dec;19(4):262-76.
doi: 10.5863/1551-6776-19.4.262.

Developmental pharmacokinetics in pediatric populations

Hong Lu  1 , Sara Rosenbaum  1
Affiliations
Review

Developmental pharmacokinetics in pediatric populations

Hong Lu et al. J Pediatr Pharmacol Ther. 2014 Oct-Dec.

Abstract

Information on drug absorption and disposition in infants and children has increased considerably over the past 2 decades. However, the impact of specific age-related effects on pharmacokinetics, pharmacodynamics, and dose requirements remains poorly understood. Absorption can be affected by the differences in gastric pH and stomach emptying time that have been observed in the pediatric population. Low plasma protein concentrations and a higher body water composition can change drug distribution. Metabolic processes are often immature at birth, which can lead to a reduced clearance and a prolonged half-life for those drugs for which metabolism is a significant mechanism for elimination. Renal excretion is also reduced in neonates due to immature glomerular filtration, tubular secretion, and reabsorption. Limited data are available on the pharmacodynamic behavior of drugs in the pediatric population. Understanding these age effects provide a mechanistic way to identify initial doses for the pediatric population. The various factors that impact pharmacokinetics and pharmacodynamics mature towards adult values at different rates, thus requiring continual modification of drug dose regimens in neonates, infants, and children. In this paper, the age-related changes in drug absorption, distribution, metabolism, and elimination in infants and children are reviewed, and the age-related dosing regimens for this population are discussed.

Keywords: cytochrome P450; development; pediatrics; pharmacodynamics; pharmacokinetics.

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Figures

Figure 1.
Figure 1.
Developmental profiles of major hepatic cytochrome P450s (A) and CYP3A7 (B). The postnatal evolution of P450 isoforms was explored in a liver bank comprising samples from fetus, neonates, infants, and adults. Isoform enzyme activity was characterized by the following measurements: methoxyresorufin demethylation (MEROD) for CYP1A2, tolbutamide hydroxylation and immunoprotein for CYP2C9, diazepam N-demethylation and immunoprotein for 2C19, dextromethorphan O-demethylation and immunoprotein for CYP2D6, chlorzoxazone hydroxylation for CYP2E1, testosterone 6beta-hydroxylation for CYP3A4, DHEA 16alpha-hydroxylation for CYP3A7. N.D., not detectable. (Data are adapted from Ref. 40–,47).
Figure 2.
Figure 2.
Developmental changes of renal glomerular filtration rate (GFR) measured by mannitol clearance. (Data adapted from Ref. 71,72).
See this image and copyright information in PMC

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