Pharmacological problems in the management of epilepsy in children.

Rational prescribing of anti-epilepsy drugs in children may be complicated by a number of problems, which include: (i) difficulties in arriving rapidly at a syndromic diagnosis, at least in some cases, with consequent uncertainties about therapeutic management; (ii) difficulties in evaluating drug response in young age groups, particularly with respect to subjective side-effects affecting cognitive function; (iii) the vulnerability of infants and children to specific aspects of drug toxicity, such as liver damage induced by valproic acid or behavioural disorders caused by barbiturates; and (iv) the need to adjust dosage to account for age-dependent pharmacokinetic changes. In particular, it is known that the rate of drug metabolism changes markedly during development. Metabolic drug elimination is often reduced at birth, but drug metabolizing enzymes mature rapidly and biotransformation in infants and children usually occurs at a faster rate than in adults. The elimination of drug which are excreted unchanged in urine appears to be less influenced by age in paediatric patients, though impairment in renal drug clearance may be seen in newborns. Monitoring of serum drug concentrations may be helpful for dosage adjustments, but it is not a substitute for careful clinical observation.