Pharmacokinetics of daptomycin during low-flow continuous renal replacement therapy in critically ill Japanese patients.

INTRODUCTION

Daptomycin is used to treat systemic and life-threatening infections caused by methicillin-resistant Staphylococcus aureus in critically ill patients receiving continuous renal replacement therapy (CRRT). However, the pharmacokinetics of daptomycin during low-flow CRRT have not been examined; thus, the appropriate dosing adjustment in Japan remains uncertain.

METHODS

The daptomycin concentrations in plasma and effluent samples of adult Japanese patients receiving continuous venovenous hemodiafiltration (n = 4) and continuous venovenous hemodialysis (n = 2) were measured by liquid chromatography. The data were analyzed and used to estimate pharmacodynamic exposure and concentrations to profile daptomycin regimens.

RESULTS

The pharmacokinetics of daptomycin was described using two-compartment model. In the six CRRT patients (effluent flow rate, 0.825 ± 0.038 L/h), the parameter estimates were: volume of distribution of the central compartment, 8.09 ± 3.76 L; volume of distribution of the peripheral compartment, 6.23 ± 2.58 L; intercompartmental clearance, 4.63 ± 1.98 L/h; total clearance, 0.439 ± 0.172 L/h; sieving coefficient, 0.0995 ± 0.0295; extrinsic clearance by CRRT, 0.0815 ± 0.0223 L/h; intrinsic clearance of the patient, 0.357 ± 0.173 L/h; area under the concentration-time curve (AUC) for 24 h, 597.6 ± 196.1 mg‧h/L. Simulated daptomycin regimen for the exposure target (AUC ≥666 mg‧h/L) was 5.36 ± 2.46 mg/kg every 24 h, achieving the safety target (the minimum concentration ≤24.3 mg/L).

CONCLUSION

These results help to define the pharmacokinetics of daptomycin during low-flow CRRT, while also helping to consider dosing regimens for critically ill Japanese patients receiving CRRT.