Pharmacology: Pharmacodynamics: The bactericidal action of vancomycin, a tricyclic glycopeptide antibiotic, results primarily from inhibition of cell-wall biosynthesis. In addition, vancomycin alters bacterial cell membrane permeability and RNA synthesis. It is bactericidal against a number of aerobic and anaerobic gram-positive microorganisms and it is synergistic when combined with another antibiotic.
Pharmacokinetics: Absorption: In subjects with healthy kidney function, multiple IV dosing of vancomycin 1 g (15 mg/kg) infused over 60 minutes produces mean plasma concentrations of approximately 63 mcg/mL immediately after the completion of infusion, mean plasma concentrations of approximately 23 mcg/mL 2 hours after infusion, and mean plasma concentrations of approximately 8 mcg/mL 11 hours after the end of the infusion.
Multiple dosing of 500 mg infused over 30 minutes produces mean plasma concentrations of about 49 mcg/mL at the completion of infusion, mean plasma concentrations of about 19 mcg/mL 2 hours after infusion, and mean plasma concentrations of about 10 mcg/mL 6 hours after infusion. The plasma concentrations during multiple dosing are similar to those after a single dose.
Distribution: Vancomycin is approximately 55% serum protein bound as measured by ultrafiltration at vancomycin serum concentrations of 10 to 100 mcg/mL. The distribution coefficient is from 0.3 to 0.43 L/kg. After IV administration of vancomycin, inhibitory concentrations are present in pleural, pericardial, ascitic, and synovial fluid; in urine, in peritoneal dialysis fluid; and in atrial appendage tissue. Vancomycin dose not readily diffuse across healthy meninges into the spinal fluid, but when meninges are inflamed, penetration into the spinal fluid occurs.
Metabolism/excretion: The mean elimination half-life of vancomycin from plasma is 4 to 6 hours in subjects with healthy renal function. In the first 24 hours, about 75% of an administered dose of vancomycin is excreted in urine by glomerular filtration. Mean plasma clearance is about 0.058 L/kg/h, and mean renal clearance is about 0.048 L/kg/h. There is no apparent metabolism of the drug.