Daptomycin pharmacokinetics were evaluated for burn patients. Burn patients had decreases in the maximum concentration of the drug in serum (44%) and the area under the concentration-time curve (47%) and increases in the volume of distribution (64%) and total clearance (77%) compared to healthy volunteers. In burn patients, daptomycin at 10 to 12 mg/kg of body weight/day would be required to achieve drug exposures similar to those for healthy volunteers receiving 6 mg/kg.Daptomycin is a novel lipopeptide antibiotic with potent in vitro activity against gram-positive bacteria, including antimicrobial-resistant strains (10). Daptomycin is approved for the treatment of complicated skin and skin structure infections and bloodstream infections, including right-sided endocarditis caused by methicillin-susceptible and -resistant Staphylococcus aureus strains. Patients with thermal burn injury are at risk of developing burn wound infections and bacteremia caused by gram-positive organisms, including drug-resistant organisms (11). Evaluation of the effect of burn injury on the deposition of daptomycin is essential to appropriate dosing in this special population. The purpose of this study was to describe daptomycin pharmacokinetics for patients with thermal burn injury and compare those parameters with those previously reported for healthy volunteers.(These data were presented in part at the 47th Interscience Conference on Antimicrobial Agents and Chemotherapy, San Francisco, CA, September 2007.) This was an open-label, single-center, pharmacokinetic study in patients with Ն18% body surface area burns who were at least 7 days after burn injury and had completed their initial fluid resuscitation. The study was approved by the Committee for the Protection of Human Subjects, the Institutional Review Board for the University of Texas Health Science Center at Houston. Patients were excluded if their actual body weight was Ͼ30% of their ideal body weight for height or if they had serum glutamic pyruvic transaminase or serum glutamic oxaloacetic transaminase values of Ն4 times the upper normal limit of normal, creatine phosphokinase values of Ն5 times the upper limit of normal, or estimated creatinine clearance of Յ30 ml/min or were receiving continuous renal replacement therapy. Patients received a single 30-min intravenous infusion of 6 mg of daptomycin/kg of body weight based on the patient's actual body weight via infusion pump. Plasma samples were obtained at 0.5, 1, 2, 4, 8, 12, and 24 h after the start of the infusion. Serum samples were obtained at 1, 2, and 8 h to determine protein binding. All urine was collected and refrigerated from drug administration through 48 h after dosing. All samples were stored at Ϫ70°C until analysis.Daptomycin plasma and urine concentrations were analyzed using reverse-phase high-performance liquid chromatography with UV detection at 220 nm over a range of concentrations from 2 to 100 g/ml (7). The intrarun percent coefficients of variation for the low-quality control of 4 g/ml and the h...