Pharmacokinetics of vancomycin in normal subjects and in patients with reduced renal function

Abstract

Recent novel clinical applications of vancomycin have stimulated reinvestigations of the pharmacologic properties of this drug. Absorption from the gastrointestinal tract is negligible, and oral administration is appropriate only for patients with certain staphylococcal and clostridial diarrheas. After intravenous administration (the intramuscular route being painful), vancomycin is excreted by glomerular filtration, with virtually total recovery in the urine. Distribution is consistent with a three-compartment open pharmacokinetic model. Serum half-life values are usually greater than 8 min in the distribution phase, 30 min to 1.5 hr in the intermediate phase, and between 5 and 11 hr in the elimination phase. The level of binding to human serum proteins is 55%. Since the relation between the vancomycin clearance and the creatinine clearance (but not the level of creatinine in serum) is linear in both normal and impaired renal function, a nomogram has been prepared that delineates dosages that will produce a mean steady-state concentration in serum of 15 micrograms/ml. Vancomycin penetrates well into pericardial, pleural, synovial, and ascitic fluid in humans, but concentrations in cerebrospinal fluid after parenteral administration may be insufficient for the successful treatment of certain cases of meningitis.