PAEDIATRIC PHARMACOTHERAPY - PHARMACOKINETICS
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Newborn or neonate (birth to 1 month)
Infant (1 to 12 month)
Young child (1 to 5 yrs)
Older child (6 to 12 yrs)
Adolescent (13 to 18 yrs)
DIFFERENCES BETWEEN CHILDREN AND ADULTS
 the pharmacokinetics and pharmacodynamics of a drug may differ between adults and
children
 these differences are mainly due to the physiological and biochemical differences
between infants, children, adolescents and adults
 there are clear difference between neonates and older infants and children.
ABSORPTION
from the GI tract is reduced in neonates, and may be reduced in children
 reduced gastric acid secretion (increased gastric pH):
- increases bioavailability of acid-labile drugs (eg, penicillin)
- decreases bioavailability of weakly acidic drugs (eg, phenobarbital)
 reduced bile salt formation decreases bioavailability of lipophilic drugs (eg, diazepam)
 reduced gastric emptying
 reduced gastric emptying and intestinal motility increase the time it takes to reach
therapeutic concentrations (infants < 3 months)
transdermal absorption may be enhanced in neonates and young infants because:
- the stratum corneum is thin
- the ratio of surface area to weight is much greater than for older children and adults.
DISTRIBUTION
 low plasma protein concentrations and higher body water composition can change
drug distribution.
 albumin and total protein concentrations approach adult levels by 10 to 12 months
 the volume of distribution Vd of many drugs is often markedly increased in the
neonate, because of:
- reduced plasma protein binding (both to albumin and to alpha-1-acid glycoprotein)
- an increased volume of extracellular fluid relative to total body water
METABOLISM
Phase I activity is:
 reduced in neonates,
 increases progressively during the first 6 months of life,
 exceeds adult rates by the 1st few years for some drugs (eg. theophylline)
 slows during adolescence,
 usually attains adult rates by late puberty.
Phase II metabolism varies considerably by substrate
 maturation of enzymes responsible for bilirubin and acetaminophen conjugation is
delayed.
ELIMINATION
Renal elimination
 plasma protein binding, renal blood flow, GFR, and tubular secretion are altered in the
1st 2 years of life
 renal plasma flow is:
- low at birth (12 ml/min)
- reaches adult levels of 140 ml/min by age 1 year
 glomerular filtration rate GFR is:
- 2 to 4 ml/min at birth,
- increases to 8 to 20 ml/min by 2 to 3 days,
- reaches adult levels of 120 ml/min by 3 to 5 months
DRUG DOSING
 because of the above factors, drug dosing in children < 12 yr is always a function of age,
body weight, or both
 this approach is practical but not ideal; even within a population of similar age and weight,
drug requirements may differ
 thus, when it’s possible, dose adjustments should be based on plasma drug concentration
(therapeutic drug monitoring TDM)