Evaluation of aminoglycoside pharmacokinetics in postpartum patients using Bayesian forecasting

Many postpartum women have suboptimal serum concentrations after standard doses of aminoglycosides. The purpose of this study was to characterize the pharmacokinetics of aminoglycosides in postpartum patients through the use of Bayesian forecasting and to test the ability of these subpopulation parameters to predict actual aminoglycoside serum concentrations. In phase I, 28 postpartum patients who received empiric gentamicin therapy were identified and Bayesian subpopulation parameters generated. In phase II, additional gentamicin concentrations (peaks and troughs) were evaluated to test bias and precision of Bayesian subpopulation versus traditional estimates in predicting actual aminoglycoside serum concentrations. In phase I, 56 gentamicin serum concentrations in 28 patients, (age, 26 +/- 7 years; actual body weight [ABW], 84.3 +/- 18.4 kg; ideal body weight [IBW], 54.6 +/- 5.1 kg; dosing weight [DW], 66.3 +/- 9.4 kg; creatinine clearance [Clcr], 140.4 +/- 34.0 ml/min / 1.73 m2), were evaluated to calculate subpopulation pharmacokinetic parameters of volume of distribution (Vd) 0.29 +/- 0.07 l/kg (DW); elimination rate constant (ke) 0.29 +/- 0.05 h-1 and half-life (t1/2) 2.5 +/- 0.5 hours. In phase II, 50 gentamicin serum concentrations in 25 patients (age, 23 +/- 4 years; ABW 79.4 +/- 17.5 kg; IBW 55.0 +/- 7.3 kg; DW 64.8 +/- 9.6 kg; Clcr 139.7 +/- 29.3 ml/min/1.73 m2) were evaluated to calculate subpopulation pharmacokinetic parameters of Vd 0.30 +/- 0.04 l/kg (DW); ke 0.27 +/- 0.06 h-1; and t1/2 2.9 +/- 0.8 hours. Predictive performance tests (95% confidence intervals) demonstrate that subpopulation postpartum Bayesian parameters show greater precision for peak concentrations and less bias for trough concentrations than do traditional population estimates (p < 0.05). Definition of the Bayesian subpopulation parameters will allow us to dose aminoglycosides optimally in postpartum patients who have fragmented data.