Tigecycline-broad spectrum antibiotic and its pharmacology.

DESCRIPTION :

Tigecycline is a glycylcycline antibiotic developed and marketed by Wyeth under the brand name Tygacil. It was given a U.S. Food and Drug Administration (FDA) fast-track approval and was approved on June 17, 2005. It was developed in response to the growing prevalence of antibiotic resistance in bacteria such as Staphylococcus aureus.

CATEGORY  :

Anti-Bacterial Agents

Tetracyclines

Antibacterials for Systemic Use

Antiinfectives for Systemic Use

PHARMACODYNAMICS :

Tigecycline is the first clinically-available drug in a new class of antibiotics called the glycylcyclines. Glycylcyclines are a new class of antibiotics derived from tetracycline. These tetracycline analogues are specifically designed to overcome two common mechanisms of tetracycline resistance, namely resistance mediated by acquired efflux pumps and/or ribosomal protection. Glycylcycline antibiotics have a similar mechanism of action as tetracycline antibiotics. Both classes of antibiotics bind to the 30S ribosomal subunit to prevent the amino-acyl tRNA from binding to the A site of the ribosome. However, the glycylcyclines appear to bind more effectively than the tetracyclines.

MECHANISM OF ACTION :

Tigecycline, a glycylcycline, 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. Tigecycline carries a glycylamido moiety attached to the 9-position of minocycline. The substitution pattern is not present in any naturally occurring or semisynthetic tetracycline and imparts certain microbiologic properties to tigecycline. Tigecycline is not affected by the two major tetracycline resistance mechanisms, ribosomal protection and efflux. Accordingly, tigecycline has demonstrated in vitro and in vivo activity against a broad spectrum of bacterial pathogens. There has been no cross resistance observed between tigecycline and other antibiotics. Tigecycline is not affected by resistance mechanisms such as beta-lactamases (including extended spectrum beta-lactamases), target site modifications, macrolide efflux pumps or enzyme target changes (e.g. gyrase/topoisomerase). In vitro studies have not demonstrated antagonism between tigecycline and other commonly used antibacterial drugs. In general, tigecycline is considered bacteriostatic.

PHARMACOKINETIC PROPERTY :

               

Protein binding  :              71% to 89%

Metabolism       

Tigecycline is not extensively metabolized. In vitro studies with tigecycline using human liver microsomes, liver slices, and hepatocytes led to the formation of only trace amounts of metabolites. A glucuronide, an N-acetyl metabolite, and a tigecyclineepimer (each at no more than 10% of the administered dose) are the primary metabol

Half life 27-43 hours

Toxicity

Since glycylcyclines are similar to tetracyclines, they share many of the same side effects and contraindications as tetracyclines. These side effects may include nausea/vomiting, headache, photosensitivity, discoloration of growing teeth, and fetal damage.

DRUG-DRUG INTERACTION :     

Warfarin +Tigecycline :

The serum concentration of Warfarin can be increased when it is combined with Tigecycline.

THERAPEUTIC USES :

Prophylaxis and treatment of nutritional vit D deficiency.

Metabolic rickets

Post menopausal osteoporosis

Hypoparathyrodism

SIDE EFFECT  :

Cough or hoarseness

dizziness

fever or chills

headache

lower back or side pain

pain, warmth, or burning in the fingers, toes, and legs

painful or difficult urination

problems with vision or hearing

Less common:

Abdominal or stomach pain

accumulation of pus

bloating or swelling of the face, arms, hands, lower legs, or feet

changes in skin color

confusion

REFERENCE:-Tripathi K D"Essential of medical pharmacology",7th edition ,page no.733,738-39.