Xtenda Mechanism of Action

Pharmacology: Pharmacodynamics: Mechanism of Action: Ceftriaxone like other cephalosporin and penicillins, kills bacteria by inhibiting mucopeptide synthesis and hence interfere with the synthesis of the bacterial cell wall. Ceftriaxone binds with high affinity to penicillin binding proteins in the bacterial cell wall, thus interfering with peptidoglycan synthesis. Peptidoglycan is a hetropolymeric structure that provides a cell with mechanical stability. The final stage in the synthesis of peptidoglycan involves a completion of the cross linking and the terminal glycine residue of the pentaglycine bridge is linked to the fourth residue of the penta-peptide(D-alanine). The transpeptidase enzyme that performs this step is inhibited by cephalosporins and penicillins. As a result the bacterial cell wall is weakened and the cell swell and then ruptures.
Ceftriaxone is bactericidal against a broad spectrum of bacteria at easily achievable plasma concentrations.
Ceftriaxone is a third generation cephalosporin which has a broad spectrum of activity against aerobic Gram Positive and Gram Negative organisms. Sensitive organisms are generally killed by a concentration of Ceftriaxone of 8 mg/L or less white resistant organisms can survive concentrations of 64 mg/L.
Pharmacokinetics: Ceftriaxone is administered as intravenous and intramuscular injection. The mean elimination half-life in healthy adults is about 6-9 hours and is thus much longer than any other Cephalosporins or cephamycins. The half life does not alter with changes in the route of administration and was only slightly to moderately affected in patients with decreased renal function and relatively normal non renal elimination, but was increased in neonates and in patients over 75 years of age.
Ceftriaxone was completely absorbed following IM administration with mean maximum plasma concentrations occurring between 2 and 3 hours post dosing. Multiple IV or IM doses ranging from 0.5 to 2 gm at 12- to 24- hour intervals resulted in 15% to 36% accumulation of ceftriaxone above single dose values.
33% to 67% of a ceftriaxone was excreted in the urine as unchanged drug and the remainder was secreted in the bile and ultimately found in the feces as microbiologically inactive compounds. After a 1 gm IV dose, average concentrations of ceftriaxone, determined from 1 to 3 hours after dosing, were 581 mcg/mL in the gall bladder bile, 788 mcg/mL in the common duct bile, 898 mcg/mL in the cystic duct bile, 78.2 mcg/gm in the gall bladder wall and 62.1 mcg/mL in the concurrent plasma.
The drug is highly protein bound (95%), demonstrating distinctly nonlinear concentration-dependent binding, with 5% free drug at levels <70 mg/L with this fraction increased to 16% at 300 mg/L, 26.5% at 500 mg/L and 42% at 600 mg/L. This however has little clinical reference.
30 minutes after infusions of 0.5, 1.0 and 2.0 gm, mean peak plasma concentrations were 82,151 and 257 mg/L respectively. 2 hours after intramuscular injection, mean peak plasma concentrations were around half of those after intravenous administration of an equivalent dose.