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Influence of Burns on Pharmacokinetics and Pharmacodynamics of Drugs Used in the Care of Burn Patients
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Influence of Burns on Pharmacokinetics and Pharmacodynamics of Drugs Used in the Care of Burn Patients
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Journal Article
Influence of Burns on Pharmacokinetics and Pharmacodynamics of Drugs Used in the Care of Burn Patients
2008
Overview
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 α
1
-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 α
1
-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.
Publisher
Springer International Publishing,Adis international,Wolters Kluwer Health, Inc,Springer Nature B.V
Subject
/ Anesthetics - pharmacokinetics
/ Animals
/ Anti-Infective Agents - pharmacokinetics
/ Anti-Infective Agents - pharmacology
/ Anti-Ulcer Agents - pharmacokinetics
/ Anti-Ulcer Agents - pharmacology
/ Anticonvulsants - pharmacokinetics
/ Anticonvulsants - pharmacology
/ Biological and medical sciences
/ Burns
/ Cyclosporine - pharmacokinetics
/ Drug Administration Schedule
/ Humans
/ Immunosuppressive Agents - pharmacokinetics
/ Immunosuppressive Agents - pharmacology
/ Medicine
/ Neuromuscular Nondepolarizing Agents - pharmacokinetics
/ Neuromuscular Nondepolarizing Agents - pharmacology
/ Pharmacokinetics. Pharmacogenetics. Drug-receptor interactions
/ Pharmacology. Drug treatments
