Major Physiologic Variations In Pediatrics

In the past, the statement that 'children are not little people' dominated research thinking. In general, both in children and in the elderly, drugs and biological products behave similarly to that in the 18-65 year-old population, although this expectation must be adjusted for age-related differences in pharmacokinetic variables, such as immature or aging enzyme metabolism systems as well as elimination rates affected by immature or aging organs of excretion.

In neonates, the gastric pH is biphasic, being high in the first few days after birth and decreasing by day 30, but it takes 5-12 years for the adult pattern and value to emerge (Signer and Fridrich 1975). On the other hand, the methylation pathway, unimportant in adults, is well developed in children. Furthermore, acetaminophen is less toxic to children than to adults, probably because it utilizes the sulphate metabolic pathway (Rane 1992).

Most infants are slow acetylators and may accumulate toxic levels of those drugs that are metabolized by this second phase of metabolism route. Renal perfusion and glomerular filtration rates (GFR) vary: for the premature, 2-4ml/min; for neonates, 25ml/min; and by 1-1.5 years old, 125 ml/min, which is equivalent to adult clearance rates (Arant 1978). The potential toxic implication of renal metabolites and elimination of unchanged drug in the very young are obvious (Stewart and Hampton 1987).

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