Elimination of Piperacillin and Tazobactam by Renal Replacement Therapies with AN69 and Polysulfone Hemofilters: Evaluation of the Sieving Coefficient

Arzuaga, Alazne; Isla, Arantxazu; Rodríguez-Gascón, Alicia; Maynar, Javier; Corral, Esther; Pedraz, José Luís

doi:10.1159/000092921

Cited by 25 publications

(15 citation statements)

References 63 publications

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“…Water-based models have been suggested to predict CRRT drug clearance [22,23] . However, these models may be inaccurate for drugs exhibiting high plasma protein binding, like daptomycin.…”

Section: Discussionmentioning

confidence: 99%

“…However, these models may be inaccurate for drugs exhibiting high plasma protein binding, like daptomycin. Other in vitro models [23] have added bovine albumin to water models to simulate protein binding, but drugs may bind to plasma proteins other than albumin. Plasmabased models have also been suggested to determine drug clearance in CRRT in vitro models [23] , but drugs may partition into red blood cells, and red blood cells may affect the dynamics of drug removal at the hemodiafilter membrane [24] .…”

Section: Discussionmentioning

confidence: 99%

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Daptomycin Clearance during Modeled Continuous Renal Replacement Therapy

Churchwell

Pasko²,

Mueller³

2006

Blood Purif

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Background/Aims: Pharmacotherapy in critically ill patients receiving continuous renal replacement therapies (CRRT) is challenging due to the lack of published information to base dosing regimens. Methods: Daptomycin’s transmembrane clearance during continuous hemofiltration and hemodialysis was assessed using an in vitro model with AN69 and polysulfone hemodiafilters at varying ultrafiltrate and dialysate flow rates (1, 2, 3 and 6 l/h). Results: During continuous hemofiltration, mean daptomycin sieving coefficient ranged from 0.14 to 0.20. Transmembrane clearances were significantly different between filter types for ultrafiltration rates of 2, 3 and 6 l/h. For continuous hemodialysis, mean daptomycin saturation coefficient ranged from 0.05 to 0.15. AN69-based daptomycin clearances were significantly lower than polysulfone values at dialysate flow rates of 2, 3 and 6 l/h. Conclusion: The extent of daptomycin’s transmembrane clearance is dependent on hemodiafilter type, dialysate and ultrafiltration rates. CRRT with high ultrafiltrate or dialysate rates may result in substantial daptomycin clearances.

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“…Water-based models have been suggested to predict CRRT drug clearance [22,23] . However, these models may be inaccurate for drugs exhibiting high plasma protein binding, like daptomycin.…”

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Daptomycin Clearance during Modeled Continuous Renal Replacement Therapy

Churchwell

Pasko²,

Mueller³

2006

Blood Purif

View full text Add to dashboard Cite

show abstract

“…Until now, there have been only small trials and case reports describing very limited elimination during continuous venovenous hemofiltration (CVVHF) using polyethersulfone and polysulfone membranes as well as interventional lung assistance (14,15). There are, however, no data available describing elimination of micafungin during continuous venovenous hemodiafiltration (CVVHDF) nor data available when using the commonly employed AN69 membrane, which is often used in the treatment of critically ill patients in Europe (16). Additionally, critically ill patients often exhibit changes in drug metabolism as well as volume of distribution.…”

mentioning

confidence: 99%

Micafungin Plasma Levels Are Not Affected by Continuous Renal Replacement Therapy: Experience in Critically Ill Patients

Vossen

Knafl

Haidinger³

et al. 2017

Antimicrob Agents Chemother

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Critically ill patients often experience acute kidney injury and the need for renal replacement therapy in the course of their treatment in an intensive care unit (ICU). These patients are at an increased risk for candidiasis. Although there have been several reports of micafungin disposition during renal replacement therapy, to this date there are no data describing the elimination of micafungin during high-dose continuous venovenous hemodiafiltration with modified AN69 membranes. The aim of this prospective open-label pharmacokinetic study was to assess whether micafungin plasma levels are affected by continuous hemodiafiltration in critical ill patients using the commonly employed AN69 membrane. A total of 10 critically ill patients with micafungin treatment due to suspected or proven candidemia were included in this trial. Prefilter/postfilter micafungin clearance was measured to be 46.0 ml/min (Ϯ21.7 ml/min; n ϭ 75 individual time points), while hemofilter clearance calculated by the sieving coefficient was 0.0038 ml/min (Ϯ0.002 ml/min; n ϭ 75 individual time points). Total body clearance was measured to be 14.0 ml/min (Ϯ7.0 ml/min; n ϭ 12). The population area under the curve from 0 to 24 h (AUC 0 -24 ) was calculated as 158.5 mg · h/liter (Ϯ79.5 mg · h/liter; n ϭ 13). In spite of high protein binding, no dose modification is necessary in patients receiving continuous venovenous hemodiafiltration with AN69 membranes. A dose elevation may, however, be justified in certain cases. (This study has been registered at ClinicalTrials.gov under identifier NCT02651038.)

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“…S C is calculated by dividing the drug concentration in the ultrafiltrate by that in the plasma (18). Drug removal during CHD has been studied for several antibiotics (2,22,46,48,49), and the clearance is described as a product, S d ϫ Q D , where S d is the saturation coefficient calculated by dividing the drug concentration in the dialysate by that in the plasma and Q D is the flow rate of the dialysate. Both S C and S d depend on the plasma unbound fraction (f P ) (31).…”

mentioning

confidence: 99%

Proposal of a Pharmacokinetically Optimized Dosage Regimen of Antibiotics in Patients Receiving Continuous Hemodiafiltration

Yamamoto

Yasuno

Katada

et al. 2011

Antimicrob Agents Chemother

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The aim of the study was to quantitatively predict the clearance of three antibiotics, amikacin, vancomycin, and teicoplanin, during continuous hemodiafiltration (CHDF) and to propose their optimal dosage in patients receiving CHDF. For this goal, in vitro CHDF experiments with a polyacrylonitrile (PAN) membrane were first performed using these antibiotics, and then the clearances were compared with in vivo CHDF situations determined in 16 critically ill patients. The in vitro CHDF clearances were described as the product of the outflow rate of a drain (Q outflow ) and the drug unbound fraction in artificial plasma, indicating that drug adsorption to the PAN membrane has minor effect on drug clearance in our settings. The observed in vivo clearances also agreed very well with the predicted values, with a product of Q outflow and plasma unbound fraction, when residual creatinine clearance (CL CR ) was taken into account (within a range of 0.67-to 1.5-fold for 15 of 16 patients). Based on these results, a nomogram of the optimized dosages of amikacin, vancomycin, and teicoplanin was proposed, and it was evident that Q outflow and residual CL CR are major determinants of the dosage and dosing interval for these antibiotics. Although the applicability needs to be confirmed with another type of membrane or higher Q outflow , our nomogram can help determine the dosage setting in critically ill patients receiving CHDF.

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Elimination of Piperacillin and Tazobactam by Renal Replacement Therapies with AN69 and Polysulfone Hemofilters: Evaluation of the Sieving Coefficient

Cited by 25 publications

References 63 publications

Daptomycin Clearance during Modeled Continuous Renal Replacement Therapy

Daptomycin Clearance during Modeled Continuous Renal Replacement Therapy

Micafungin Plasma Levels Are Not Affected by Continuous Renal Replacement Therapy: Experience in Critically Ill Patients

Proposal of a Pharmacokinetically Optimized Dosage Regimen of Antibiotics in Patients Receiving Continuous Hemodiafiltration

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