CLINICAL PHARMACOKINETICS IN PATIENTS WITH BURNS

Burn injury induces many different pathological changes in the human b ody, which potentially alter pharmacokinetic parameters such as bioava ilability, protein binding, volume of distribution (Vd) and clearance. The extent of these alterations depends on the drug, the type and ext ent of injury and the time that elapsed between injury and drug admini stration. Bioavailability of large and hydrophilic molecules may be in creased because of enhanced intestinal permeability. The free fraction of a drug in plasma can be increased (when primarily bound to albumin ) or decreased (when primarily bound to alpha(1)-acid glycoprotein). V d may change as a consequence of altered protein binding or an enlarge d extracellular fluid volume. Alterations in clearance may be due to c hanges in glomerular filtration, tubular secretion, hepatic blood flow , drug-metabolising activity, protein binding and to the presence of a dditional elimination pathways. Elimination half-life changes when Vd and/or clearance is affected following burn injury. The therapeutic co nsequences of pharmacokinetic alterations are discussed in principle, and for specific treatment with antibacterials, anti-ulcer drugs, anal gesics, muscle relaxants, anxiolytics, phenytoin and cyclosporin. If s ignificant changes in pharmacokinetic disposition occur following ther mal injury, therapeutic drug monitoring and dosage adjustment may be r equired to ensure rational and well tolerated drug therapy in patients with burns. Future studies should focus on the impact of specific pat ient variables (e.g, type of injury and size of burn) on the extent of pharmacokinetic alterations.