High variability of teicoplanin concentration in patients with continuous venovenous hemodiafiltration

Abstract

INTRODUCTION: Continuous venovenous hemodiafiltration (CVVHDF) may alter teicoplanin pharmacokinetics and increase the risk of incorrect dosing. The objective of this prospective observational study was to assess the effect of CVVHDF on the pharmacokinetics of teicoplanin as maintenance therapy. METHODS: Blood, urine, and dialysate samples were collected to measure teicoplanin levels. CVVHDF clearance (CLCVVHDF ), total clearance (CLTOTAL ), and volume of distribution (Vd) were calculated by simplex-linear modeling. The influence of CVVHDF dose on teicoplanin pharmacokinetics was assessed. FINDINGS: Ten samples from eight patients were studied. Creatinine clearance was 3.4 +/- 5.1 ml/min/1.73 m(2) . Three patients were anuria. The dose for CVVHDF was 32.1 +/- 7.0 mL/kg/h. Vd was 1.6 +/- 0.7 L/kg. T1/2 was 100.1 +/- 42.7 hours. CLTOTAL of teicoplanin was 11.9 +/- 5.4 mL/min and CLCVVHDF was 5.8 +/- 4.2 mL/min. Contribution of CLCVVHDF to CLTOTAL was 51.2% +/- 23.6%. CLCVVHDF of individual teicoplanin varied widely. Large intra-occasion differences were also observed. Dose of CLCVVHDF did not influence overall CLTOTAL , Vd, or half-life. The proportion of CLTOTAL due to CLCVVHDF varied widely. It was high in some cases. DISCUSSION: In patients receiving CVVHDF, there is great variability in teicoplanin pharmacokinetics which complicates empiric approach to dosing, suggesting the need for therapeutic drug monitoring.