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Pharmacokinetic/pharmacodynamic profile for tigecycline-a new glycylcycline antimicrobial agent.

Abstract：

:Tigecycline is a new first-in-class glycylcycline antimicrobial agent with expanded broad-spectrum activity against both Gram-negative and Gram-positive aerobes and anaerobes, as well as atypical bacterial species. The spectrum of activity extends to clinically relevant susceptible and multidrug-resistant strains of Staphylococcus aureus, Streptococcus pneumoniae, vancomycin-resistant enterococci, and Enterobacteriaceae, including extended-spectrum beta-lactamase-producing strains. Tigecycline is administered as an intravenous formulation and has been studied in the treatment of serious polymicrobial infections, including complicated skin and skin-structure infections and intra-abdominal infections. Pharmacokinetic analysis of data from phase 1 trials of healthy subjects indicate that tigecycline has a large volume of distribution, signifying extensive tissue penetration, and a long terminal elimination half-life (approximately 40 h), easily allowing for twice-daily dose administration. Tigecycline penetrates well into blister fluid, which supports the positive findings of phase 2 and 3 studies of the efficacy of tigecycline in the treatment of serious skin and skin-structure infections. Metabolic studies in humans have revealed that tigecycline undergoes very limited metabolism and the primary route of elimination of unchanged drug is through the feces, with glucuronidation and renal elimination as secondary routes. A preliminary pharmacokinetic (PK)/pharmacodynamic analysis in experimental animal models of infection indicates that the efficacy of tigecycline is probably best predicted by the ratio of the area under the concentration-time curve to the minimum inhibitory concentration. The expanded in vitro activity against a broad range of bacteria, including resistant pathogens, and favorable PK profile of tigecycline suggest that this novel antimicrobial agent should offer clinicians an option for the treatment of patients with serious bacterial infections.

journal_name

Diagn Microbiol Infect Dis

journal_title

Diagnostic microbiology and infectious disease

authors

Meagher AK,Ambrose PG,Grasela TH,Ellis-Grosse EJ

doi

10.1016/j.diagmicrobio.2005.05.006

subject

Has Abstract

pub_date

2005-07-01 00:00:00

pages

165-71

issue

3

eissn

0732-8893

issn

1879-0070

pii

S0732-8893(05)00133-1

journal_volume

52

pub_type

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