Clin Pharmacokinet
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Bone infection has long been a formidable foe of orthopaedic surgeons. The standard method of treating osteomyelitis generally consists of irrigation and debridement supplemented by pre- and postoperative antibiotics and intraoperative antimicrobial solutions. In the 1970s, Buchholz introduced the concept of local antibacterial therapy in the form of antibiotic impregnated bone cement to treated infected arthroplasties. ⋯ This makes the use of antibiotic-impregnated polymethylmethacrylate (PMMA) beads highly effective either as an alternative to, or in conjunction with, systemic antibiotic treatment of infected arthroplasties, and localised bone and soft tissue infection. This article explores the indications for the use of local therapy as well as any advantages or disadvantages it may have over systemic antibacterial treatment. Additionally, there are important pharmacokinetic considerations for the optimal use of antibacterial agents in the treatment of osteomyelitis.
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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 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.