期刊
INTERNATIONAL JOURNAL OF ANTIMICROBIAL AGENTS
卷 25, 期 6, 页码 523-529出版社
ELSEVIER SCIENCE BV
DOI: 10.1016/j.ijantimicag.2005.02.013
关键词
tigecycline; steady-state; pulmonary pharmacokinetics
资金
- NCRR NIH HHS [M01 RR 00079] Funding Source: Medline
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 100 mg loading dose followed by six 50 mg 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/MIC90; AUC/MIC90), and percentage time above MIC90 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 forserurn were 0.72 +/- 0.24 mu g/mL, 1.73 +/- 0.64 mu g*h/mL and 15.0 +/- 1.10 h; for lung epithelial lining fluid (ELF) the values were 0.37 mu g/mL, 2.28 mu g*h/mL and 39.1 h; and for alveolar cells (AC) were 15.2 mu g/mL, 134 mu g*h/mL and 23.7 h. Tigecycline was concentrated in AC: C-max/MIC90 ratios ranged from 30.4 (H. influenzae) to 507 (S. pneumoniae); AUC/MIC90 ratios ranged from 268 (H. influenzae) to 4467 (S. pneumoniae); and percentage dose interval above MIC90 was 100% for the five respiratory pathogens. The C-max/MIC90, AUC/MIC90 ratios, T > MIC90 and extended serum and intrapulmonary half-lives following the regimen used in this study are favourable for the treatment of tigecycline-susceptible pulmonary infections. (c) 2005 Elsevier B.V. and the International Society of Chemotherapy. All rights reserved.
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