Vancomycin 500 mg · Dry-powder injectables

Vancomycin is an antibacterial drug [see Microbiology (12.4)].

General Pharmacokinetics — In subjects with normal kidney function, multiple intravenous dosing of 1 g of vancomycin (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 those after a single dose.

In healthy subjects administered a single 1g dose of TYZAVAN, geometric mean (geometric %CV) AUC0-inf values for NADA and vancomycin were 209 (19.6%) and 219 (13.7%) mcg*h/mL, respectively. Based on a population pharmacokinetic analysis, 1g TYZAVAN administered over 1.5 hours every 12 hours achieves a geometric mean (95% prediction interval) steady state AUC0-24 exposure of 383 (277-547) and 382 (261-567) mcg*h/mL for NADA and vancomycin in healthy subjects, respectively.

Distribution — The distribution coefficient is from 0.3 to 0.43 L/kg. Vancomycin is approximately 55% serum protein bound as measured by ultrafiltration at vancomycin serum concentrations of 10 to 100 mcg/mL. After intravenous administration of vancomycin, inhibitory concentrations are present in pleural, pericardial, ascitic, and synovial fluids; in urine; in peritoneal dialysis fluid; and in atrial appendage tissue. Vancomycin does not readily diffuse across normal meninges into the spinal fluid; but, when the meninges are inflamed, penetration into the spinal fluid occurs.

Elimination — Mean plasma clearance is about 0.058 L/kg/h, and mean renal clearance is about 0.048 L/kg/h. The mean elimination half-life of vancomycin from plasma is 4 to 6 hours in subjects with normal renal function. In anephric patients, the mean elimination half-life is 7.5 days. Total systemic and renal clearance of vancomycin may be reduced in the elderly.

Metabolism — There is no apparent metabolism of the vancomycin.

Excretion — In the first 24 hours, about 75% of an administered dose of vancomycin is excreted in urine by glomerular filtration. Renal dysfunction slows excretion of vancomycin.

In the first 48 hours after intravenous administration of a single 1 g dose of TYZAVAN, the percent excreted unchanged in urine was approximately 80% for NADA.