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Influence of Burns on Pharmacokinetics and Pharmacodynamics of Drugs Used in the Care of Burn Patients

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Abstract

The pharmacokinetics and pharmacodynamics of drugs are significantly altered in the burn patient, and the burn patient population shows wide inter- and intraindividual variation in drug handling. Burn injury evolves in two phases. The first phase corresponds to the burn shock, which occurs during the first 48 hours after thermal injury. In this phase, hypovolaemia, oedema, hypoalbuminaemia and a low glomerular filtration rate are observed, which result in a slower rate of drug distribution and lower renal clearance. The second phase (beyond 48 hours after injury) is a hyperdynamic state with high blood flow in the kidneys and liver, an increased α1-acid-glycoprotein level and loss of the drug with exudate leakage. As a result, protein binding, drug distribution and clearance may be altered.

Because of the alteration in these variables, wide intraindividual variation of pharmacokinetic parameters occurs depending upon the time since thermal injury and fluid resuscitation. Interindividual variations may be correlated with the percentage of the body surface area that is burnt, creatinine clearance, albuminaemia or the α1-acid-glycoprotein level. A number of important variations in pharmacodynamic parameters have been described, but their mechanisms are poorly understood.

From a practical point of view, for the subpopulation of burn patients who eliminate drugs extremely rapidly, higher doses and/or shorter dosing intervals are required to avoid treatment inefficacy. Drug concentration measurements help to take into account interindividual variability. However, adaptation of doses based on Bayesian methods is frequently not possible because the distribution of pharmacokinetic parameters is poorly characterized in this population. Methods based only on individual data or on a surrogate marker for efficacy may be used to optimize the dosing regimen in this population.

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No sources of funding were used to assist in the preparation of this review. The authors have no conflicts of interest that are directly relevant to the content of this review.

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Authors and Affiliations

  1. Department of Pharmacy-Toxicology, GH Cochin-Saint Vincent-de-Paul, Paris, France

    Benoit Blanchet &  Michel Tod

  2. Department of Clinical Pharmacology, GH Cochin-Saint Vincent-de-Paul, Université Paris Descartes, Paris, France

    Vincent Jullien

  3. Intensive Care Unit, GH Cochin-Saint Vincent-de-Paul, Université Paris Descartes, Paris, France

    Christophe Vinsonneau

  4. Université de Lyon, F-69008, Lyon, France

    Michel Tod

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  1. Benoit Blanchet
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Correspondence to Michel Tod.

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Blanchet, B., Jullien, V., Vinsonneau, C. et al. Influence of Burns on Pharmacokinetics and Pharmacodynamics of Drugs Used in the Care of Burn Patients. Clin Pharmacokinet 47, 635–654 (2008). https://doi.org/10.2165/00003088-200847100-00002

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