Treating disorders of the neonatal central nervous system: pharmacokinetic and pharmacodynamic considerations with a focus on antiepileptics

A major consideration in the treatment of neonatal disorders is that the selected drug, dose and dosage frequency is safe, effective and appropriate for the intended patient population. Thus, a thorough knowledge of the pharmacokinetics and pharmacodynamics of the chosen drug within the patient popu...

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Bibliographic Details
Published in:British journal of clinical pharmacology Vol. 81; no. 1; pp. 62 - 77
Main Authors: Donovan, Maria D., Boylan, Geraldine B., Murray, Deirdre M., Cryan, John F., Griffin, Brendan T.
Format: Journal Article
Language:English
Published: England John Wiley and Sons Inc 01.01.2016
Subjects:
Anticonvulsants - pharmacokinetics
Anticonvulsants - pharmacology
antiepileptics
Blood-Brain Barrier
Brain - metabolism
Central Nervous System Diseases - drug therapy
Humans
Infant, Newborn
Infant, Newborn, Diseases - drug therapy
Models, Biological
neonate
patient‐specific computational modeling
pharmacodynamics
pharmacokinetics
Review
Reviews
pharmacokinetics
neonate
antiepileptics
patient-specific computational modeling
pharmacodynamics
ISSN:0306-5251, 1365-2125, 1365-2125
Online Access:Get full text
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Summary:A major consideration in the treatment of neonatal disorders is that the selected drug, dose and dosage frequency is safe, effective and appropriate for the intended patient population. Thus, a thorough knowledge of the pharmacokinetics and pharmacodynamics of the chosen drug within the patient population is essential. In paediatric and neonatal populations two additional challenges can often complicate drug treatment – the inherently greater physiological variability, and a lack of robust clinical evidence of therapeutic range. There has traditionally been an overreliance in paediatric medicine on extrapolating doses from adult values by adjusting for bodyweight or body surface area, but many other sources of variability exist which complicate the choice of dose in neonates. The lack of reliable drug dosage data in neonates has been highlighted by regulatory authorities, as only ~50% of the most commonly used paediatric medicines have been examined in a paediatric population. Moreover, there is a paucity of information on the pharmacokinetic parameters which affect drug concentrations in different body tissues, and pharmacodynamic responses to drugs in the neonate. Thus, in the present review, we draw attention to the main pharmacokinetic factors that influence the unbound brain concentration of neuroactive drugs. Moreover, the pharmacodynamic differences between neonates and adults that affect the activity of centrally‐acting therapeutic agents are briefly examined, with a particular emphasis on antiepileptic drugs.
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ISSN:0306-5251
1365-2125
1365-2125
DOI:10.1111/bcp.12753