title: PK/PD analysis of biapenem in patients undergoing continuous hemodiafiltration.
abstract: BACKGROUND
  Continuous hemodiafiltration (CHDF) is used as renal replacement therapy for critically ill patients with renal failure, and to treat hypercytokinemia. Since CHDF also clears therapeutic agents, drug pharmacokinetics (PK) should be dependent upon CHDF conditions. Although the antibiotic biapenem (BIPM) is used in patients undergoing CHDF, the optimal therapeutic regimen in such patients has not been fully clarified. In this study, we investigated the PK of BIPM in patients with various levels of renal function undergoing CHDF with polysulfone (PS) membrane, and used PK models to identify the optimal administration regimen.
  
  
  METHODS
  BIPM (300 mg) was administered by infusion in patients undergoing CHDF (n = 7). Blood and filtrate-dialysate were collected for compartment and non-compartment analysis.
  
  
  RESULTS
  The sieving coefficient of PS membrane was 1.00 ± 0.06 (mean ± S.D., n = 7), and CHDF clearance of BIPM was found to be the sum of the dialysate flow rate (QD) and filtrate flow rate (QF). Non-CHDF clearance showed inter-individual variability (4.82 ± 2.48 L/h), depending on residual renal function and non-renal clearance. Based on the average PK parameters obtained with a compartmental model, maximal kill end point (over 40 % T > MIC4 μg/mL) was achieved with regimens of 300 mg every 6 h, 300 mg every 8 h, and 600 mg every 12 h. Monte Carlo simulation indicated that 300 mg infusion for 1 h every 6 h was optimal, and the probability of target attainment at MIC2 μg/mL was 90.2 %.
  
  
  CONCLUSIONS
  Our results establish the optimal regimen of BIPM in patients with various levels of renal function undergoing CHDF with a PS membrane.
authors.affiliation: Department of Medicinal Informatics, Graduate School of Medical Sciences, Kanazawa University, 13-1 Takara-machi, Kanazawa, 920-8640 Japan ; Department of Hospital Pharmacy, University Hospital, Kanazawa University, 13-1 Takara-machi, Kanazawa, 920-8641 Japan.
authors.forename: Gaku
authors.initials: G
authors.lastname: Akashita
authors.affiliation: Department of Hospital Pharmacy, University Hospital, Kanazawa University, 13-1 Takara-machi, Kanazawa, 920-8641 Japan ; School of Pharmacy, College of Medical, Pharmaceutical and Health Sciences, Kanazawa University, Kakuma-machi, Kanazawa, 920-1192 Japan.
authors.forename: Yuto
authors.initials: Y
authors.lastname: Hosaka
authors.affiliation: Intensive Care Unit, University Hospital, Kanazawa University, 13-1 Takara-machi, Kanazawa, 920-8641 Japan.
authors.forename: Toru
authors.initials: T
authors.lastname: Noda
authors.affiliation: Department of Hospital Pharmacy, University Hospital, Kanazawa University, 13-1 Takara-machi, Kanazawa, 920-8641 Japan.
authors.forename: Kazuya
authors.initials: K
authors.lastname: Isoda
authors.affiliation: Department of Medicinal Informatics, Graduate School of Medical Sciences, Kanazawa University, 13-1 Takara-machi, Kanazawa, 920-8640 Japan ; Department of Hospital Pharmacy, University Hospital, Kanazawa University, 13-1 Takara-machi, Kanazawa, 920-8641 Japan.
authors.forename: Tsutomu
authors.initials: T
authors.lastname: Shimada
authors.affiliation: Department of Medicinal Informatics, Graduate School of Medical Sciences, Kanazawa University, 13-1 Takara-machi, Kanazawa, 920-8640 Japan ; Department of Hospital Pharmacy, University Hospital, Kanazawa University, 13-1 Takara-machi, Kanazawa, 920-8641 Japan.
authors.forename: Kazuki
authors.initials: K
authors.lastname: Sawamoto
authors.affiliation: Department of Medicinal Informatics, Graduate School of Medical Sciences, Kanazawa University, 13-1 Takara-machi, Kanazawa, 920-8640 Japan ; Department of Hospital Pharmacy, University Hospital, Kanazawa University, 13-1 Takara-machi, Kanazawa, 920-8641 Japan.
authors.forename: Ken-Ichi
authors.initials: K
authors.lastname: Miyamoto
authors.affiliation: Intensive Care Unit, University Hospital, Kanazawa University, 13-1 Takara-machi, Kanazawa, 920-8641 Japan.
authors.forename: Takumi
authors.initials: T
authors.lastname: Taniguchi
authors.affiliation: Department of Medicinal Informatics, Graduate School of Medical Sciences, Kanazawa University, 13-1 Takara-machi, Kanazawa, 920-8640 Japan ; Department of Hospital Pharmacy, University Hospital, Kanazawa University, 13-1 Takara-machi, Kanazawa, 920-8641 Japan.
authors.forename: Yoshimichi
authors.initials: Y
authors.lastname: Sai
keywords: Biapenem; Continuous hemodiafiltration; Monte Carlo simulation; PK/PD breakpoint; Pharmacokinetics
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