The pharmacokinetics of tigecycline, when given as a 100-mg loading dose followed by 50 mg every 12 h, were determined in serum and blister fluid. The peak tigecycline concentration and half-life in serum were greater than those in blister fluid. Tigecycline penetrates into blister fluid well, with a mean penetration rate of 74%.Tigecycline is the first of the glycylcyclines, a novel class of antimicrobials structurally related to the tetracyclines, to undergo clinical development (19). Tigecycline is an expanded broad-spectrum antibiotic with activity against gram-negative, gram-positive, anaerobic, and atypical pathogens. It shows in vitro activity against tetracycline-resistant organisms containing genes responsible for efflux or ribosomal protection resistance mechanisms, as well as other resistant pathogens, such as methicillin-resistant Staphylococcus aureus and Staphylococcus epidermidis, penicillin-resistant Streptococcus pneumoniae, and vancomycin-resistant enterococci (1,2,5,6,12).Limited pharmacokinetic data are available for tigecycline, and no studies evaluating tigecycline's ability to penetrate the skin have been published. In phase 2 studies, tigecycline has demonstrated good clinical efficacy in the treatment of skin and skin structure infections (17).In the context of skin and soft tissue infections, the evaluation of drug concentrations by using the cantharidin-induced skin blister model mimics situations within an infected tissue (13). Previous studies using this model have been successfully performed at the Center for Anti-Infective Research and Development, Hartford Hospital (14). The purpose of this study was to determine the steady-state pharmacokinetic profile of tigecycline in serum and blister fluid when tigecycline is administered intravenously over 30 min as a 100-mg loading dose followed by 50 mg every 12 h for a total of seven doses.This study was approved by Hartford Hospital's Institutional Review Board. All subjects were given a detailed description of the study, and all provided written informed consent. Ten healthy subjects were enrolled in this single-center, multipledose, open-label study. The subjects were 20 to 37 years of age (mean age, 26.7 years), 172 to 185 cm in height (mean height, 177.3 cm), and 69.5 to 89.1 kg in weight (mean weight, 80.1 kg). Participation included a screening evaluation within 3 weeks of tigecycline administration on day 1 and a 6-day (5-night) inpatient period. Subjects were enrolled after the screening evaluation, and laboratory evaluations (including hematologies, blood chemistries, and urinalyses) and electrocardiograms revealed no clinically significant abnormalities.Each subject received a loading dose of 100 mg of tigecycline (Wyeth Pharmaceuticals, Collegeville, Pa.) infused over 30 min on study day 1, followed by 50 mg infused over 30 min every 12 h, for a total of seven doses. Subjects were served mediumfat meals approximately 30 min before tigecycline administration. Fluids were allowed ad libitum. Consumption of any caffeine-containin...
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