Mechanism of Action
The combination works by synergistic mechanism of inhibition of bacterial cell wall synthesis. Ceftriaxone enters into bacterial cell wall space of the vancomycin resistant bacteria i.e. PBPs which include transpeptidase, glycosyltransferase, and carboxypeptidases. Ceftriaxone bind to PBPs and inhibit the transpeptidation step of peptidoglycan synthesis to stop bacterial cell wall growth. Ceftriaxone-induced increased permeability in the peptidoglycan layer increases the penetrability of the vancomycin and restores (to some extent) its affinity towards the exposed D-alanine moieties of NAM-NAG peptides. The ‘double blow’ caused by the components of Vancoplus makes bacterial cell more susceptible to death.
Absorption: The maximum plasma concentration of ceftriaxone and vancomycin after 60 min intravenous infusion of 1.5 g Vancoplus was 135.4 μg/ml and 47 μg/ml, respectively. Intravenous dosing of 3.0 g Vancoplus infused over 60 min produces mean plasma concentrations of approximately 270.8 μg/ml and 94 μg/ml of ceftriaxone and vancomycin, respectively. Ceftriaxone reached maximum concentration in 0.5 h and vancomycin immediately after the dose in above two doses.
Distribution: Ceftriaxone and vancomycin distributes well in various compartments including extra-vascular spaces, tissue fluid, pleural, pericardial, peritoneal, ascitic, synovial fluid of inflamed joints and also passes the placental barrier. Ceftriaxone is reversibly bound to albumin and the binding is 95 % at plasma concentrations less than 100 mg/L. Vancomycin has been found to be approximately 10-50 % reversibly bound to human serum protein. The volume of distribution (Vd) for ceftriaxone and vancomycin are 7-12 l and 12-84 L respectively.
Metabolism: Ceftriaxone does not undergo systemic metabolism but it is broken down in the small intestine by bacterial action. There is no apparent metabolism of the vancomycin.
Elimination: Approximately 50–60% of ceftriaxone and 80-90% of vancomycin is eliminated as an unchanged active substance in the urine whilst the remainder is excreted via the bile into the faeces as microbiologically inactive metabolites