Drug metabolism for the paediatrician

Abstract

Drug metabolism importantly determines drug concentrations. The efficacy and safety of many drugs prescribed for children are, therefore, dependent on intraindividual and interindividual variation in drug-metabolising enzyme activity. During growth and development, changes in drug-metabolising enzyme activity result in age-related differences in drug disposition, most pronounced in preterm infants and young infants. The shape of the developmental trajectory is unique to the drug-metabolising enzyme involved in the metabolism of individual drugs. Other factors impacting drug metabolism are underlying disease, drug-drug interactions and genetic variation. The interplay of age with these other factors may result in unexpected variation in drug metabolism in children of different ages. Extrapolation of adult data to guide drug dosing in children should be done with caution. The younger the child, the less reliable is the extrapolation. This review aims to identify the primary sources of variability of drug metabolism in children, the knowledge of which can ultimately guide the practitioner towards effective and safe drug therapy.

Adverse Drug Reactions Across the Age Continuum: Epidemiology, Diagnostic Challenges, Prevention, and Treatments

“…Patterns of expression of drug metabolizing enzymes over the first year of life. Modified from de Wildt et al …”

Theoretical pharmacokinetic drug alterations in pediatric celiac disease

“…Additional dosing approaches include body-surface-areabased dosing --which does not accurately reflect size, and allometric scaling which also has disadvantages [14,18]. In recognition of the limitations with pediatric dosing, we briefly describe the ADME changes in childhood ontogeny for a better understanding of how celiac disease may augment these processes.…”

“…Acetaminophen is frequently used in children and is a substrate of UGT1A6 and to a lesser extent, UGT1A9. The glucuronidation of morphine, another common pediatric drug and substrate of UGT2B7, can be detected in newborns and reaches adult levels by 12 months of age [18].…”

Dosage Adjustments Related to Young or Old Age and Organ Impairment

“…Age is a primary influence on drug disposition. Substantial changes in organ function and enzyme processes that occur before and after birth through completion of puberty have major influences on drug disposition . Because age and body size are usually highly correlated, including organ size and functional capacity, age is a strong indicator of drug disposition …”