Dosing optimization of meropenem based on a pharmacokinetic analysis in patients receiving hemodiafiltration and an in vitro model.

The purpose of this study was to estimate the in vivo pharmacokinetics of meropenem during intermittent-infusion hemodiafiltration (I-HDF) and clarify its optimal dosage and dosing interval in patients receiving I-HDF. The clearance of meropenem by online hemodiafiltration (OL-HDF) and I-HDF was predicted using an in vitro system and assessed to establish whether the results obtained are applicable to clinical cases. In the in vivo study, the mean volume of distribution (Vd), non-I-HDF clearance (CL _non-I-HDF ), and I-HDF clearance (CL _I-HDF ) were 15.80 ± 3.59 l, 1.05 ± 0.27 l/h, and 5.78 ± 1.03 l/h. Dosing regimens of 0.25 g once daily for a MIC of 8 μg/ml and of 0.5 g once daily for a MIC of 16 μg/ml achieved 40% T > MIC. In the in vitro and in vivo studies, observed CL _HDF was similar to predictive CL _HDF (= C _f /C _p  × (Q _D  + Q _SUB )). In conclusion, adjustments to the dose and interval of meropenem were developed based on the presumed susceptibility of pathogens to meropenem in patients receiving I-HDF. We suggest 0.5 g once daily as an appropriate regimen for empirical treatment.
(Copyright © 2017 Japanese Society of Chemotherapy and The Japanese Association for Infectious Diseases. Published by Elsevier Ltd. All rights reserved.)