Clinical Pharmacokinetics and Pharmacodynamics of Tigecycline

Abstract

Rapid emergence of resistance against antibacterials emphasizes the need for the development of novel and/or more potent antibacterials. Tigecycline is the first representative of a new drug class, the glycylcyclines, and was approved in 2005 by the US FDA for the treatment of complicated skin and skin structure infections, as well as complicated intra-abdominal infections. Tigecycline distributes extensively into the intracellular space of tissue and accumulates in cells, which may qualify it for the treatment of intracellular infections. The pharmacokinetics of tigecycline are complex with both linear and non-linear characteristics. The reason for this complexity is still not fully understood. Non-linearity can be found in the volume of distribution possibly due to extensive and variable tissue and/or plasma protein binding. In contrast, clearance and area under the plasma concentration-time curve are dose-independent. Tigecycline has a high incidence of mild adverse effects, mainly nausea and vomiting, but is otherwise well tolerated.

Population Pharmacokinetics of Tigecycline in Critically Ill Patients with Severe Infections

“…The fAUC 0 -24 /MIC breakpoint for efficacy was Ͼ0.9, but fAUC 0 -24 was calculated as AUC 0 -24 ϫ fu, where fu is the fraction of unbound tigecycline, which was assumed to be 0.2 (9). However, tigecycline shows atypical nonlinear plasma protein-binding behavior, so assuming a fixed plasma protein-binding value may be problematic, when this value may range from 71% to 89% (13). Therefore, we used total AUC 0 -24 /MIC targets in this study, although we concede that it would have been preferable to measure unbound concentrations.…”

Tigecycline Is Highly Efficacious against Mycobacterium abscessus Pulmonary Disease

“…The peripheral compartments of 8 HFSs were each inoculated with 20 ml of 6 log 10 CFU/ml M. abscessus. Treatment was administered daily for 21 days at doses that mimicked the non-proteinbound or free AUC 0 -24 , peak concentrations, and times to maximum concentration achieved in the lungs of humans treated with tigecycline doses of 0, 12.5, 25, 50, 100, 200, 400, and 800 mg, assuming linear increases in AUC 0 -24 with dose since clearance is constant over a range of doses (14)(15)(16). The doses were administered to the central compartment of each HFS once daily via computerized syringe pumps.…”

Experiencia con el uso compasivo de tigeciclina en pacientes pediátricos infectados por Klebsiella pneumoniae productora de carbapenemasas

“…Otro de los diagnósticos que justificó su uso fue la neumonía; tigeciclina tiene adecuadas concentraciones en el parénquima pulmonar y adecuada penetración a las células alveolares 2 . Se debió utilizar en bacteriemia, con el conocimiento Experiencia Clínica que tigeciclina alcanza concentraciones séricas modestas 8,18 , obteniéndose en uno de dos pacientes un curso clínico favorable. Esto puede explicarse en parte por la reducción del inóculo bacteriano en la fuente primaria de la infección y por el uso concomitante de otros antimicrobianos, algunos de los cuales demostraron susceptibilidad in vitro, pero es importante aclarar que este tipo de reportes no es suficiente para confirmar este tipo de hipótesis.…”

“…Existen numerosos reportes en la literatura médica que describen la utilidad in vitro de tigeciclina contra microorganismos multi-resistentes 4 , incluyendo K. pneumoniae productora de carbapenemasas (Kpn KPC) 5,6 . Hasta el momento tigeciclina está aprobada en adultos para el tratamiento de infecciones de tejidos blandos, infecciones intra-abdominales y neumonía adquirida en la comunidad 7,8 ; no obstante, su actividad frente a bacterias multi-resistentes le confiere un promisorio papel en el tratamiento de otras infecciones en las que se sospeche o demuestre la presencia de este tipo de bacterias.…”