Dosing and therapeutic monitoring of phenytoin in young adults after neurotrauma: are current practices relevant?
Anticonvulsant drugs are commonly used to treat and prevent seizures after neurotrauma. However, many physiological changes occur in the neurotrauma patient, which alter the pharmacokinetics of drugs such as phenytoin. This raises concerns relating to the dosage and monitoring of phenytoin in these patients compared with its routine use in epileptic patients. Examples of pharmacokinetic alterations within the neurotrauma patient include changes in hepatic metabolism, protein binding alterations, and disruption of the blood-brain barrier. Drug interactions and genetic factors may also contribute to pharmacokinetic variations. Many studies have reported that neurotrauma patients often present with either subtherapeutic or highly variable phenytoin serum concentrations. When phenytoin doses recommended for the epileptic patient are used in the neurotrauma patient, efficacy is limited to early posttraumatic seizures, with no effect on morbidity, mortality, or the onset of late posttraumatic seizures. This review examines the effect of neurotrauma on the pharmacokinetics of phenytoin alongside clinical outcomes and questions the current dosing and therapeutic monitoring practices within this area.
Frend
Vivien
V
Faculty of Pharmacy, University of Sydney, NSW, Australia.
Chetty
Manoranjenni
M
D000927:Anticonvulsants / Q000493:pharmacokinetics / Q000627:therapeutic use*; D001812:Blood-Brain Barrier / Q000187:drug effects; D001930:Brain Injuries / Q000150:complications*; D006801:Humans; D008099:Liver / Q000187:drug effects / Q000378:metabolism; D010672:Phenytoin / Q000493:pharmacokinetics / Q000627:therapeutic use*; D011485:Protein Binding / Q000187:drug effects; D012640:Seizures / Q000188:drug therapy* / Q000209:etiology*; D013997:Time Factors; D016896:Treatment Outcome
D000927:Anticonvulsants; D010672:Phenytoin