Penetration of micafungin into the burn eschar in patients with severe burns
Burn injury induces many different pathological changes in the human body, which potentially alter pharmacokinetic parameters such as bioavailability, protein binding, volume of distribution (Vd) and clearance. The extent of these alterations depends on the drug, the type and extent of injury and the time that elapsed between injury and drug administration. Bioavailability of large and hydrophilic molecules may be increased 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). Vd may change as a consequence of altered protein binding or an enlarged extracellular fluid volume. Alterations in clearance may be due to changes in glomerular filtration, tubular secretion, hepatic blood flow, drug-metabolising activity, protein binding and to the presence of additional elimination pathways. Elimination half-life changes when Vd and/or clearance is affected following burn injury. The therapeutic consequences of pharmacokinetic alterations are discussed in principle, and for specific treatment with antibacterials, anti-ulcer drugs, analgesics, muscle relaxants, anxiolytics, phenytoin and cyclosporin. If significant changes in pharmacokinetic disposition occur following thermal injury, therapeutic drug monitoring and dosage adjustment may be required to ensure rational and well tolerated drug therapy in patients with burns. Future studies should focus on the impact of specific patient variables (e.g. type of injury and size of burn) on the extent of pharmacokinetic alterations.