title: Steady-state serum and intrapulmonary pharmacokinetics and pharmacodynamics of tigecycline.
abstract: The steady-state serum and intrapulmonary pharmacokinetic and pharmacodynamic parameters of tigecycline were determined after intravenous administration in 30 subjects. Tigecycline was administered as a 100mg loading dose followed by six 50mg doses given every 12h and was measured using HPLC/mass spectrometry. Ratios of tigecycline maximum serum concentration and area under the serum concentration-time curve to 90%-minimum inhibitory concentrations (C(max)/MIC(90); AUC/MIC(90)), and percentage time above MIC(90) were calculated for common respiratory pathogens (Streptococcus pneumoniae, Chlamydia pneumoniae, Mycoplasma pneumoniae, Moraxella catarrhalis and Haemophilus influenzae). The C(max) (mean+/-S.D.), AUC and half-life for serum were 0.72+/-0.24 microg/mL, 1.73+/-0.64 microg*h/mL and 15.0+/-1.10h; for lung epithelial lining fluid (ELF) the values were 0.37 microg/mL, 2.28 microg*h/mL and 39.1h; and for alveolar cells (AC) were 15.2 microg/mL, 134 microg*h/mL and 23.7h. Tigecycline was concentrated in AC: C(max)/MIC(90) ratios ranged from 30.4 (H. influenzae) to 507 (S. pneumoniae); AUC/MIC(90) ratios ranged from 268 (H. influenzae) to 4467 (S. pneumoniae); and percentage dose interval above MIC(90) was 100% for the five respiratory pathogens. The C(max)/MIC(90), AUC/MIC(90) ratios, T>MIC(90) and extended serum and intrapulmonary half-lives following the regimen used in this study are favourable for the treatment of tigecycline-susceptible pulmonary infections.
authors.affiliation: Infectious Diseases Research Group, Department of Epidemiology & Biostatistics, University of California-San Francisco, 500 Parnassus Avenue, Box 560, San Francisco, CA 94117, USA. jconte@itsa.ucsf.edu
authors.forename: John E
authors.initials: JE
authors.lastname: Conte
authors.forename: Jeffrey A
authors.initials: JA
authors.lastname: Golden
authors.forename: Mary Grace
authors.initials: MG
authors.lastname: Kelly
authors.forename: Elisabeth
authors.initials: E
authors.lastname: Zurlinden
mesh_terms: D000900:Anti-Bacterial Agents / Q000008:administration & dosage / Q000493:pharmacokinetics* / Q000494:pharmacology*; D019540:Area Under Curve; D001419:Bacteria / Q000187:drug effects*; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry; D002851:Chromatography, High Pressure Liquid; D006207:Half-Life; D006801:Humans; D007275:Injections, Intravenous; D008168:Lung / Q000737:chemistry*; D013058:Mass Spectrometry; D008826:Microbial Sensitivity Tests; D008911:Minocycline / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000097:blood / Q000493:pharmacokinetics / Q000494:pharmacology; D011650:Pulmonary Alveoli / Q000737:chemistry; D015610:Serum Bactericidal Test; D000078304:Tigecycline
chemical_list: D000900:Anti-Bacterial Agents; D000078304:Tigecycline; D008911:Minocycline