Non steady state and steady state PKS Bayesian forecasting and vancomycin pharmacokinetics in ICU adult patients

The pharmacokinetics of vancomycin was investigated in adult ICU patients a fter the first administration and at steady stare. Then the predictive perf ormance of a two-compartment Bayesian forecasting program was assessed in t hese patients by using population-based parameters and three non steady sta te vancomycin concentrations as feedback information. Finally a prospective investigation was carried out to search potential covariates, At steady st ate, a significant decrease (around 30%) in clearance (CL) was observed, wh ile creatinine clearance (CLcr) was stable and a significant increase (arou nd 30%) in volume of distribution (Vss) was observed. A two-fold increase i n elimination half-life was found. CL was weakly correlated with CLcr at on set of therapy and at steady state. The Bayesian program tended to overpred ict vancomycin peak and trough concentrations. A larger mean prediction err or and a poorer precision were observed when population-based parameter est imates were used (no feedback) compared to feedback prediction, but the dif ferences were not significant. Mechanical ventilation and concurrent opioid therapy may be pertinent covariates of vancomycin pharmacokinetics. The cu rrent work has shown that vancomycin pharmacokinetics in ICU patients displ ayed a significant variability and a significant change in both clearance a nd distribution during the course of therapy. Further investigation is nece ssary to clarify these findings. Moreover, the use of the Bayesian forecast ing PKS program in our patients led to a prediction with low bias but rathe r poor precision. This outcome highlights the need to implement a populatio n modeling approach, to determine the vancomycin pharmacokinetic parameters and covariates in our ICU patients, and to apply this information to provi de more accurate concentration predictions.