Tigilyn Mechanism of Action

Pharmacotherapeutic group: Antibacterials for systemic use, tetracyclines.
Pharmacology: Pharmacodynamics: Mechanism of Action: Tigecycline (Tigilyn), a glycylcycline antibiotic, inhibits protein translation in bacteria by binding to the 30S ribosomal subunit and blocking entry of amino-acyl tRNA molecules into the A site of the ribosome. This prevents incorporation of amino acid residues into elongating peptide chains. In general, Tigecycline (Tigilyn) is considered bacteriostatic. At 4 times the minimum inhibitory concentration (MIC), a 2-log reduction in colony counts was observed with Tigecycline (Tigilyn) against Enterococcus spp., Staphylococcus aureus, and Escherichia coli.
Pharmacokinetics: Absorption: Tigecycline (Tigilyn) is administered intravenously and therefore has 100% bioavailability.
Distribution: The in vitro plasma protein binding of Tigecycline (Tigilyn) ranges from approximately 71% to 89% at concentrations observed in clinical studies (0.1 to 1.0 mcg/mL). Animal and human pharmacokinetic studies have demonstrated that Tigecycline (Tigilyn) readily distributes to tissues.
In rats, receiving single or multiple doses of C-tigecycline, radioactivity was well distributed to most tissues, with the highest overall exposure observed in bone marrow, salivary glands, thyroid gland, spleen, and kidney. In humans, the steady-state volume of distribution of Tigecycline (Tigilyn) averaged 500 to 700 L (7 to 9 L/kg), indicating that Tigecycline (Tigilyn) is extensively distributed beyond the plasma volume and concentrates into tissues.
No data are available on whether Tigecycline (Tigilyn) can cross the blood-brain barrier in humans.
Metabolism: Tigecycline is not extensively metabolized. In vitro studies with Tigecycline (Tigilyn) using human liver microsomes, liver slices, and hepatocytes led to the formation of only trace amounts of metabolites. In healthy male volunteers, receiving C-tigecycline, Tigecycline (Tigilyn) was the primary C-labeled material recovered in urine and feces, but a glucuronide, an N-acetyl metabolite and a Tigecycline (Tigilyn) epimer (each at no more than 10% of the administered dose) were also present.
Elimination: The recovery of the total radioactivity in feces and urine following administration of 14C-tigecycline indicates that 59% of the dose is eliminated by biliary/fecal excretion, and 33% is excreted in urine. Overall, the primary route of elimination for Tigecycline (Tigilyn) is biliary excretion of unchanged Tigecycline (Tigilyn). Glucuronidation and renal excretion of unchanged Tigecycline (Tigilyn) are secondary routes.
The total clearance of Tigecycline (Tigilyn) is 24 L/h after intravenous infusion. Renal clearance is approximately 13% of total clearance. Tigecycline (Tigilyn) shows a polyexponential elimination from serum with a mean terminal elimination half-life after multiple doses of 42 hours although high inter individual variability exists.