Steady-state serum and intrapulmonary pharmacokinetics and pharmacodynamics of tigecycline

• Published in: International journal of antimicrobial agents 2005-06, Vol.25 (6), p.523-529
• Main Authors: Conte, John E., Golden, Jeffrey A., Kelly, Mary Grace, Zurlinden, Elisabeth
• Format: Article
• Language: English
• Subjects: Anti-Bacterial Agents - administration & dosage; Anti-Bacterial Agents - pharmacokinetics; Anti-Bacterial Agents - pharmacology; Antibiotics. Antiinfectious agents. Antiparasitic agents; Area Under Curve; Bacteria - drug effects; Biological and medical sciences; Bronchoalveolar Lavage Fluid - chemistry; Chromatography, High Pressure Liquid; Half-Life; Humans; Injections, Intravenous; Lung - chemistry; Mass Spectrometry; Medical sciences; Microbial Sensitivity Tests; Minocycline - administration & dosage; Minocycline - analogs & derivatives; Minocycline - blood; Minocycline - pharmacokinetics; Minocycline - pharmacology; Pharmacology. Drug treatments; Pulmonary Alveoli - chemistry; Pulmonary pharmacokinetics; Serum Bactericidal Test; Steady-state; Tigecycline
• ISSN: 0924-8579; 1872-7913
• DOI: 10.1016/j.ijantimicag.2005.02.013

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 ( 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 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: 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.