Talking To Toddlers

Positive Parenting Tips for Toddlers

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Children may exhibit different drug disposition and/or response compared to adults. The pediatric patient cannot be considered as a "little" adult. It is well documented that age-related developmental and physiological changes exist not only in the pediatric population compared to adults but also within pediatric age group. In addition, environmental (e.g., exposure to drugs in vitro) and dietary factors can affect PK of drugs [56]. FDA guidance on pediatrics and ICH E11 [57] define age groups within pediatric population. The pediatric population is categorized into the following age groups— preterm new born (gestation 23 to 34 weeks), term newborn infants (0 to 1 month), toddlers (1 to 24 months), children (2-11 years), and adolescents (12-16/18 years).

Absorption of drugs can be affected by gastric pH, gastric emptying time, and intestinal transit times. Gastric pH value is almost neutral at birth [6, 7] then starts to vary from day eight and slowly declines to reach the adult value by age three to seven years. This results in higher absorption of acid labile drugs, such as penicillin and amoxicillin in toddlers and younger children. Gastric emptying is prolonged until six months of age. Intestinal transit time is decreased in children resulting in incomplete absorption of sustained release products [58-61].

The total body water is increased and the percentage of body fat is decreased in infants and children [62]. Albumin concentrations normalize at one year of age and albumin binding is lower in infants. The concentration of AAG is also higher over the first year [63, 64]. The variability with age in these factors can affect drug binding and thus the drug distribution [65, 66]. Further, the blood brain barrier in newborn infants is not fully developed and drugs may cross the blood brain barrier resulting in CNS toxicity [56, 67].

Both Phases I and II metabolizing enzymes are not mature at the time of birth and different enzyme activity may reach the adult levels at different ages (Table 1). For example, CYP3A4 activity may reach the adult level at six months of age, whereas, CYP2D6 maturation occurs by five years and CYP1A6 by 10 years of age. In case of renal excretion, the GFR, active tubular secretion, and tubular reabsorption are lower in infants and nearly equal to adults by 12 months of age and reach adult levels by childhood.

P-glycoprotein (PGP) expression has been associated with decreased gut absorption of drugs and decreased amount of drugs crossing the blood brain barrier. However, developmental aspects of PGP have not been investigated [56]. Pharmacodynamic changes with age have been known for neuromuscular blocking agents [68, 69].

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