Population Pharmacokinetics of Vancomycin under Continuous Renal Replacement Therapy using a Polymethylmethacrylate Hemofilter.

Yamazaki, Shingo; Tatebe, Mizuki; Fujiyoshi, Masachika; Hattori, Noriyuki; Suzuki, Tatsuya; Takatsuka, Hirokazu; Uchida, Masashi; Suzuki, Takaaki; Ishii, Itsuko

BACKGROUND Although continuous hemodiafiltration (CHDF) is often performed in critically ill patients during sepsis treatment, the pharmacokinetics of vancomycin (VCM) during CHDF with a polymethylmethacrylate hemofilter (PMMA-CHDF) has not been revealed. In this study, the authors aimed to describe the population pharmacokinetics of VCM in critically ill patients undergoing PMMA-CHDF and clarify its hemofilter clearance (CLhemofilter). METHODS This single-center, retrospective study enrolled patients who underwent intravenous VCM therapy during PMMA-CHDF at the intensive care unit of Chiba University Hospital between 2008 and 2016. A population analysis was performed and CLhemofilter was assessed. RESULTS Twenty-five patients were enrolled. Median body weight (BW) and Sequential Organ Failure Assessment (SOFA) score were 63 kg and 15, respectively. Mean conditions for CHDF were 107.5 ± 18.3 mL/min for blood flow rate and 26.3 ± 6.3 mL/kg/h for effluent flow rate. The mean parameter estimates were: distribution volume of the central compartment (V1), 59.1 L; clearance of the central compartment (CL1), 1.35 L/h; distribution volume of the peripheral compartment (V2), 56.1 L; and clearance of the peripheral compartment (CL2), 3.65 L/h. BW and SOFA score were significantly associated with V1 (P < 0.05) and CL1 (P < 0.05), respectively, and were thus selected as covariates in the final model. The estimated dosage of VCM to achieve a target area under the concentration-time curve/minimum inhibitory concentration ≥ 400 was 27.1 mg/kg for loading and 9.7 mg/kg every 24 h for maintenance; these dosages were affected by BW and SOFA score. Mean CLhemofilter obtained from 8 patients was 1.35 L/h, which was similar to CL1. CONCLUSIONS The authors clarified the pharmacokinetics and CLhemofilter of VCM in PMMA-CHDF patients. The pharmacokinetics of VCM in patients undergoing CHDF appeared to vary not only with the CHDF setting and BW, but also with SOFA score.