TY - JOUR
T1 - Dosing optimization of meropenem based on a pharmacokinetic analysis in patients receiving hemodiafiltration and an in vitro model
AU - Yokoyama, Yuta
AU - Nishino, Kakine
AU - Matsumoto, Kazuaki
AU - Inomoto, Yuki
AU - Matsuda, Kaori
AU - Nakamura, Rin nosuke
AU - Yasuno, Nobuhiro
AU - Kizu, Junko
N1 - Publisher Copyright:
© 2017 Japanese Society of Chemotherapy and The Japanese Association for Infectious Diseases
Copyright:
Copyright 2018 Elsevier B.V., All rights reserved.
PY - 2018/2/1
Y1 - 2018/2/1
N2 - 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 (CLnon-I-HDF), and I-HDF clearance (CLI-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 CLHDF was similar to predictive CLHDF (= Cf/Cp × (QD + QSUB)). 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.
AB - 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 (CLnon-I-HDF), and I-HDF clearance (CLI-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 CLHDF was similar to predictive CLHDF (= Cf/Cp × (QD + QSUB)). 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.
KW - Dosing regimen
KW - Intermittent infusion hemodiafiltration
KW - Meropenem
KW - Online hemodiafiltration
KW - Prediction equation
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U2 - 10.1016/j.jiac.2017.09.005
DO - 10.1016/j.jiac.2017.09.005
M3 - Article
C2 - 29054458
AN - SCOPUS:85031498403
SN - 1341-321X
VL - 24
SP - 92
EP - 98
JO - Journal of Infection and Chemotherapy
JF - Journal of Infection and Chemotherapy
IS - 2
ER -
