Steady-state serum and intrapulmonary pharmacokinetics and pharmacodynamics of tigecycline

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 12 h 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 (Cmax/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 Cmax (mean ± S.D.), AUC and half-life for serum were 0.72 ± 0.24 μg/mL, 1.73 ± 0.64 μg*h/mL and 15.0 ± 1.10 h; for lung epithelial lining fluid (ELF) the values were 0.37 μg/mL, 2.28 μg*h/mL and 39.1 h; and for alveolar cells (AC) were 15.2 μg/mL, 134 μg*h/mL and 23.7 h. Tigecycline was concentrated in AC: Cmax/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 Cmax/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.