Pharmacokinetic alterations after severe head injury

Bradley Boucher, Scott D. Hanes

Research output: Contribution to journalArticle

45 Citations (Scopus)

Abstract

Pharmacological therapy, present and future, will undoubtedly continue to play a large role within the overall management of patients with severe head injury. Nevertheless, limited clinical data are available to evaluate the effect of severe head injury on pharmacokinetics. The disruption of the blood-brain barrier secondary to trauma and/or subsequent hyperosmolar therapy can be expected to result in higher than expected brain drug concentrations. Aggressive dietary protein supplementation may result in increased oxidative drug metabolism. These effects may counterbalance inhibitory influences on drug metabolism secondary to cytokine release during the acute phase response. Alterations in protein binding can also be anticipated with the hypoalbuminaemia and increases in α1-acid glycoprotein typically observed in these patients. Based on studies in other patient populations, moderate hypothermia, a treatment strategy in patients with head injury, can decrease drug metabolism. The pharmacokinetics of the following drugs in patients with severe head injury have been studied: phenytoin, pentobarbital (pentobarbitone), thiopental (thiopentone), tirilazad, and the agents used as marker substrates, antipyrine, lorazepam and indocynanine green (ICG). Several studies have documented increases in metabolism over time with phenytoin, pentobarbital, thiopental, antipyrine and lorazepam. Increases in tirilazad clearance were also observed but attributed to concurrent phenytoin therapy. No changes in the pharmacokinetics of ICG were apparent following head injury. With the frequent use of potent inhibitors of drug metabolism (e.g. cimetidine, ciprofloxacin) the potential for drug interaction is high in patients with severe head injury. Additional pharmacokinetic investigations are recommended to optimise pharmacological outcomes in patients with severe head injury.

Original languageEnglish (US)
Pages (from-to)209-221
Number of pages13
JournalClinical Pharmacokinetics
Volume35
Issue number3
DOIs
StatePublished - Sep 30 1998

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Craniocerebral Trauma
Pharmacokinetics
Thiopental
Phenytoin
Pentobarbital
Pharmaceutical Preparations
Antipyrine
Lorazepam
Pharmacology
Hypoalbuminemia
Acute-Phase Reaction
Dietary Proteins
Cimetidine
Therapeutics
Ciprofloxacin
Dietary Supplements
Hypothermia
Blood-Brain Barrier
Drug Interactions
Protein Binding

All Science Journal Classification (ASJC) codes

  • Pharmacology (medical)
  • Pharmacology, Toxicology and Pharmaceutics(all)

Cite this

Pharmacokinetic alterations after severe head injury. / Boucher, Bradley; Hanes, Scott D.

In: Clinical Pharmacokinetics, Vol. 35, No. 3, 30.09.1998, p. 209-221.

Research output: Contribution to journalArticle

Boucher, Bradley ; Hanes, Scott D. / Pharmacokinetic alterations after severe head injury. In: Clinical Pharmacokinetics. 1998 ; Vol. 35, No. 3. pp. 209-221.
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