Pharmacokinetics and Pharmacodynamics
Tigecycline is available for intravenous administration and is recommended to be given as a 100-mg loading dose followed by 50 mg every 12 h of maintenance dosing. Tigecycline is not extensively metabolized and is eliminated primarily unchanged in bile and feces. Plasma-protein binding of tigecycline is variable (71-87%) and has been demonstrated to be concentration dependent. Additional elimination of the active drug occurs in the urine (<30%)but dosing adjustments are not required in patients with renal insufficiency or end-stage renal disease. In patients with severe hepatic dysfunction (Child Pugh class C), systemic clearance of tigecycline is prolonged and a dosage adjustment is required (100-mg loading dose followed by 25 mg every 12 h). There is no dosage adjustment required in patients with mild-to-moderate liver dysfunction or in patients receiving hemodialysis, since tigecycline is not significantly removed.[1,3,7]
Investigations in healthy volunteers and data from clinical trials indicate that tigecycline follows linear pharmacokinetics. A summary of tigecycline's single-dose and multiple-dose pharmacokinetic parameters is presented in Table 1 .[2,7,8,9] As with, tetracycline agents, tigecycline displays time-dependent antibacterial activity. Additionally, investigations have demonstrated the presence of a post-antibiotic effect (PAE) for tigecycline in several pathogens. For instance, the PAEs for Streptococcus pneumoniae and Escherichia coli in a murine thigh-infection model were 8.9 and 4.9 h, respectively, following a 3-mg/kg intravenous tigecycline dose.
Tigecycline exhibits a large volume of distribution (7-10 l/kg) and several studies have investigated concentrations of the drug in various tissues.[9,11] One study assessed penetration to pulmonary sources by comparing achievable concentrations (ACs) to serum levels obtained at steady state. ACmax of 0.37 and 15.2 µg/ml, an area under the curve (AUC) of 2.28 and 134 µg/h/ml, and a half-life of 39.1 h and 23.7 h was demonstrated for epithelial lining fluid and alveolar cells, respectively. These investigators concluded that tigecycline concentrations were adequate for managing pulmonary infections caused by susceptible isolates.
The penetration of tigecycline to several intra-abdominal sources has also been demonstrated. Bile, gallbladder and colon concentrations were all found to be higher than serum steady-state concentrations. Also, skin blister fluid penetration following multiple tigecycline doses was 74% of the concentration found in serum.
Expert Rev Anti Infect Ther. 2008;6(5):557-567. © 2008 Expert Reviews Ltd.
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Cite this: Establishing the Role of Tigecycline in an era of Antimicrobial Resistance - Medscape - Oct 01, 2008.