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Clinical Significance of the Pharmacokinetic and Pharmacodynamic Characteristics of Tigecycline

[ Vol. 10 , Issue. 1 ]

Author(s):

Matthew E. Falagas, Drosos E. Karageorgopoulos and George Dimopoulos   Pages 13 - 21 ( 9 )

Abstract:


Tigecycline is a novel antibacterial agent with a wide spectrum of antimicrobial activity that includes pathogens with clinically significant resistance patterns. The clinical effectiveness of tigecycline has been evaluated in several non-inferiority, phase III, randomized, double-blind, controlled clinical trials regarding, mainly, complicated skin and skin structure infections and complicated intraabdominal infections. Clinical data regarding the effectiveness of tigecycline against infections caused by multidrug-resistant pathogens that commonly affect severely ill patients as well as community acquired pneumonia are favorable, yet limited. The consideration of the pharmacokinetic and pharmacodynamic properties of tigecycline may aid in further understanding the therapeutic role of this agent. Respectively, the utility of tigecycline in the treatment of severe infections involving the bloodstream has not been substantiated, particularly regarding pathogens with borderline susceptibility. Moreover, the fact that a relatively small proportion of the administered tigecycline dose is excreted unchanged in the urine may compromise the effectiveness of this agent in serious urinary tract infections. Increasing the dose of tigecycline to maximize effectiveness against severe infections appears as an appealing therapeutic option, considering the linear pharmacokinetics exhibited by this agent. However, gastrointestinal toxicity (nausea and vomiting) is usually dose-limiting. Further research is recommended on therapeutic strategies to optimize the effectiveness and safety of tigecycline therapy in severely ill patients.

Keywords:

Glycylcyclines, tetracyclines, bacterial drug resistance, sepsis, area under concentration curve, tissue distribution, half-life, metabolism

Affiliation:

Alfa Institute of Biomedical Sciences (AIBS), 9 Neapoleos Street, 151 23 Marousi, Athens, Greece.



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