Pharmacokinetic considerations in the treatment of childhood epilepsy.
Organogenesis throughout childhood affects almost every aspect of pediatric pharmacotherapy. The antiepileptic drugs (AEDs) are particularly impacted since most elimination rates are diminished for the first 6 months of infancy, but quickly attain and supersede adult values. When children enter a hypermetabolic stage, large doses of AEDs may be necessary to maintain effective serum concentrations. Medication noncompliance is frequently confused as hypermetabolism, since both present with low serum drug concentrations. Amazingly, noncompliance among children with chronic illness approaches a similar incidence to that reported in the adult population. It is obviously important to include this in the differential diagnosis of the etiology of subtherapeutic serum AED concentrations. Maturational differences also affect gastrointestinal drug absorption. Intestinal transit time and absorptive surface area are both diminished in young children. Drug delivery systems suitable in adults may not deliver the total dosage in children. Differences in the composition of body compartments and protein binding can alter the volume of drug distribution and, consequently, serum concentrations. In addition to pathophysiologic changes, there is evidence to suggest differences between a mature and immature brain. These differences include quantitative and qualitative responses to neurotransmitters. Hence, it is understandable why seizure semiology is different in children compared with adults. This constellation of factors contributes to the challenges of caring for children with epilepsy.
Gilman
Jamie T
JT
Neuroscience Clinical Affairs, Ortho-McNeil Pharmaceuticals Inc, Woodbury, Tennessee, USA. jgilman@ompus.jnj.com
Duchowny
Michael
M
Campo
Ana E
AE
D000375:Aging / Q000378:metabolism; D000927:Anticonvulsants / Q000378:metabolism / Q000493:pharmacokinetics / Q000627:therapeutic use; D001921:Brain / Q000254:growth & development*; D002648:Child; D004347:Drug Interactions; D004827:Epilepsy / Q000145:classification / Q000188:drug therapy / Q000378:metabolism; D006801:Humans; D007223:Infant; D007408:Intestinal Absorption; D014018:Tissue Distribution
D000927:Anticonvulsants