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Pharmacokinetic Considerations in the Treatment of Childhood Epilepsy

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Abstract

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.

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Acknowledgements

No sources of funding were used to assist in the preparation of this manuscript. The author has no conflicts of interest that are directly relevant to the content of this manuscript.

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Authors and Affiliations

  1. Neuroscience Clinical Affairs, Ortho-McNeil Pharmaceuticals Inc, Woodbury, Tennessee, USA

    Jamie T. Gilman

  2. Department of Neurology, Miami Children’s Hospital, Miami, Florida, USA

    Michael Duchowny

  3. Department of Psychiatry and Behavioral Sciences, University of Miami School of Medicine, Miami, Florida, USA

    Ana E. Campo

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  1. Jamie T. Gilman
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  2. Michael Duchowny
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  3. Ana E. Campo
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Correspondence to Jamie T. Gilman.

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At the time of preparation of this manuscript, Dr Gilman was affiliated to the Department of Neuroscience, Miami Children’s Hospital, Miami. Florida, USA

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Gilman, J.T., Duchowny, M. & Campo, A.E. Pharmacokinetic Considerations in the Treatment of Childhood Epilepsy. Pediatr-Drugs 5, 267–277 (2003). https://doi.org/10.2165/00128072-200305040-00005

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