PHARMACOKINETIC OPTIMIZATION OF VANCOMYCIN THERAPY

Renewed interest in vancomycin over the past decade has led to an abun dance of data concerning the pharmacokinetics of vancomycin, and its d osage selection and concentration-response relationships. No definitiv e data exist that correlate vancomycin serum concentrations with clini cal outcomes. However, inconsistencies in sampling times for peak seru m concentrations and differences in infusion times make Interpreting v ancomycin serum concentrations difficult. Furthermore, the evidence im plicating vancomycin as a cause of oto- or nephrotoxicity is circumsta ntial, and these adverse effects may occur only in high-risk populatio ns. Owing to the variability in its dose-serum concentration relations hip and mullicompartmental pharmacokinetics, several methodologies hav e been developed for instituting and adjusting vancomycin dosages. Nom ograms rely on a fixed volume of distribution and the relationship bet ween vancomycin clearance and creatinine clearance. Since both of thes e factors may be altered in certain populations, dosage methodologies (both traditional and Bayesian) that use population- or patient-specif ic pharmacokinetic data perform better than standard nomograms for ini tiating vancomycin therapy. Controversy still exists as to whether a 1 - or a 2-compartment model is more appropriate for making dosage adjus tments; however, steady-state rather than non-steady state vancomycin serum concentrations should be used for dosage adjustments. Certain pa thophysiological states such as age, bodyweight and renal function con tribute to altered pharmacokinetics and may alter the design of the do sage regimen. Since no definitive relationship exists between vancomyc in serum concentrations and either clinical outcome or adverse effects , considerable controversy surrounds the utility of monitoring serum v ancomycin concentrations. Therefore, routine vancomycin serum concentr ation monitoring may be warranted only in specific populations, such a s patients receiving concurrent aminoglycoside therapy or those receiv ing higher than usual dosages of vancomycin, patients undergoing haemo dialysis and patients with rapidly changing renal function.