Abstract
BackgroundContinuous 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.MethodsBIPM (300 mg) was administered by infusion in patients undergoing CHDF (n = 7). Blood and filtrate-dialysate were collected for compartment and non-compartment analysis.ResultsThe 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 %.ConclusionsOur results establish the optimal regimen of BIPM in patients with various levels of renal function undergoing CHDF with a PS membrane.
Highlights
Continuous hemodiafiltration (CHDF) is used as renal replacement therapy for critically ill patients with renal failure, and to treat hypercytokinemia
CHDF alters the clearance of BIPM, and Ikawa et al have reported on PK modeling and dosage adaptation of BIPM during CHDF with a polymethyl methacrylate (PMMA) membrane in patients with renal failure [18]
The sum of CLCDHFand CLnon-CHDF, calculated as (QF + Dialysate flow rate (QD)) · sieving coefficient (SC) and as k10 · V1, respectively [x], and CLtot obtained by non-compartmental analysis of the plasma BIPM concentration [y] showed a good correlation (y = 1.01 x − 0.02, r2 = 1.00), supporting the validity of the model
Summary
Continuous hemodiafiltration (CHDF) is used as renal replacement therapy for critically ill patients with renal failure, and to treat hypercytokinemia. Akashita et al Journal of Pharmaceutical Health Care and Sciences (2015) 1:31 positive, Gram-negative, and anaerobic bacteria [10] It is not cleaved by dehydropeptidase-1 (DHP-1), unlike other penem antibiotics such as panipenem and imipenem, and can be used as a single agent without the need for formulation of a nephrotoxicity-reducing agent or DHP-1 inhibitor [11,12,13]. The PK of single BIPM administration was calculated using multi-compartment models, and it was found that the dose amount and dosing interval were important factors determining the value of % of T > MIC. Their models were applicable only to patients with renal failure. The effects of other types of filter membrane in CHDF should be considered
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