Determinants of Ceftazidime Clearance by Continuous Venovenous Hemofiltration and Continuous Venovenous Hemodialysis

Matzke, Gary R.; Frye, Reginald F.; Joy, Melanie S.; Palevsky, Paul M.

doi:10.1128/aac.44.6.1639-1644.2000

Cited by 39 publications

(24 citation statements)

References 22 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Since SA is based on diffusion, SA tends to be lower than SC, especially for solutes of larger molecular weight when all CRRT parameters are held constant [5] . Furthermore, SA is also more sensitive than SC to varying Q d (or Q uf in the case of CVVH) and hemodiafilter membrane differences [5,7,30,31] . At low Q d , SA and SC should be very similar [21,30] , but as Q d increases, dialysate has less time to become saturated and SA becomes increasingly smaller than SC, especially for larger molecular weight drugs [30] .…”

Section: Discussionmentioning

confidence: 99%

“…Urea is not significantly protein bound, consequently a SC and SA of ϳ 1 would be expected and was achieved in the present study. A small amount of variability in SA and SC did occur and this could be due to differences in hemodiafilter composition and CRRT flow rates [20,26,30,31] , as well as the aforementioned possible interspecies protein-binding differences. However, at Q uf of 1 l/h the mean daptomycin Daptomycin SC and SA differences between filters were observed as Q uf and Q d increased ( tables 1 , 2 ).…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Daptomycin Clearance during Modeled Continuous Renal Replacement Therapy

Churchwell

Pasko²,

Mueller³

2006

Blood Purif

View full text Add to dashboard Cite

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.

show abstract

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

“…Discordance between Sc/Sa and protein free fraction has also been reported for other antibiotics [15,26,27] . Lau et al [37] showed that for drugs that are highly protein bound, protein binding was the primary factor limiting drug sieving, but for other drugs the presence of plasma proteins had only a modest effect on the sieving coeffi cient.…”

Section: Discussionmentioning

confidence: 93%

“…Higher as well as lower Sc/Sas than expected from protein-binding data have often been reported [10][11][12][13][14][15][16]38] . Different alternatives have been suggested to explain increased sieving coeffi cient: the requirement for the electroneutrality across the hemofi ltration membrane [26,39] , weak bindings to plasma proteins [40] or alterations of the fraction of drug available for transport across the fi lter membrane because of the passage through the extracorporeal circuit [26] . The issue of lower Scs has been much less discussed in the literature [41] ; adsorption to hemofi lter or the Gibbs-Donnan effect has been suggested [15] .…”

Section: Discussionmentioning

confidence: 99%

“…The in vitro Sc of piperacillin and tazobactam was calculated as Sc = C UF /C P , where C UF is the drug concentration in the ultrafi ltrate and C P is the drug concentration in the prefi lter port of simultaneously collected spec- imens [25,26] . Similarly, Sa was calculated as Sa = C D /C P , where C D is the drug concentration in the dialysate.…”

Section: Sieving Coeffi Cient Calculationmentioning

confidence: 99%

See 1 more Smart Citation

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

et al. 2006

View full text Add to dashboard Cite

Background/Aim: Piperacillin-tazobactam is commonly used to treat infections in ICU patients. Controversial data have been published about the sieving/saturation coefficient (Sc/Sa) of piperacillin during continuous renal replacement therapies (CRRT). The objective was to evaluate the Sc/Sa of piperacillin-tazobactam during continuous venovenous hemofiltration (CVVH) and continuous venovenous hemodialysis (CVVHD) using AN69 and polysulfone. Methods: Ringer lactate, BSA-containing Ringer lactate and plasma were circulated at 150 ml/min. The ultrafiltrate/dialysis flow was kept at 1,500 ml/min. A bolus was injected and samples were taken. Drugs were measured using HPLC. Sc/Sa was calculated according to standard formula. Results: Free passage of drugs through the membranes was reported with protein free solutions. In the presence of proteins the Sc/Sa lowered and correlated to protein free fraction. Polysulfone had a significantly higher permeability than AN69 during CVVH. Conclusion: Drug binding to albumin contributes to the decrease of the Sc/Sa of piperacillin but it does not completely justify the in vivo value obtained by some authors.

show abstract

A Monte Carlo Simulation Approach for Beta‐Lactam Dosing in Critically Ill Patients Receiving Prolonged Intermittent Renal Replacement Therapy

Jang

Gharibian

Lewis

et al. 2018

The Journal of Clinical Pharma

View full text Add to dashboard Cite

Cefepime, ceftazidime, and piperacillin/tazobactam are commonly used beta-lactam antibiotics in the critical care setting. For critically ill patients receiving prolonged intermittent renal replacement therapy (PIRRT), limited pharmacokinetic data are available to inform clinicians on the dosing of these agents. Monte Carlo simulations (MCS) can be used to guide drug dosing when pharmacokinetic trials are not feasible. For each antibiotic, MCS using previously published pharmacokinetic data derived from critically ill patients was used to evaluate multiple dosing regimens in 4 different prolonged intermittent renal replacement therapy effluent rates and prolonged intermittent renal replacement therapy duration combinations (4 L/h × 10 hours or 5 L/h × 8 hours in hemodialysis and hemofiltration modes). Antibiotic regimens were also modeled depending on whether drugs were administered during or well before prolonged intermittent renal replacement therapy therapy commenced. The probability of target attainment (PTA) was calculated using each antibiotic's pharmacodynamic target during the first 48 hours of therapy. Optimal doses were defined as the smallest daily dose achieving ≥90% probability of target attainment in all prolonged intermittent renal replacement therapy effluent and duration combinations. Cefepime 1 g every 6 hours following a 2 g loading dose, ceftazidime 2 g every 12 hours, and piperacillin/tazobactam 4.5 g every 6 hours attained the desired pharmacodynamic target in ≥90% of modeled prolonged intermittent renal replacement therapy patients. Alternatively, if an every 6-hours cefepime regimen is not desired, the cefepime 2 g pre-prolonged intermittent renal replacement therapy and 3 g post-prolonged intermittent renal replacement therapy regimen also met targets. For ceftazidime, 1 g every 6 hours or 3 g continuous infusion following a 2 g loading dose also met targets. These recommended doses provide simple regimens that are likely to achieve the pharmacodynamics target while yielding the least overall drug exposure, which should result in lower toxicity rates. These findings should be validated in the clinical setting.

show abstract

Determinants of Ceftazidime Clearance by Continuous Venovenous Hemofiltration and Continuous Venovenous Hemodialysis

Cited by 39 publications

References 22 publications

Daptomycin Clearance during Modeled Continuous Renal Replacement Therapy

Daptomycin Clearance during Modeled Continuous Renal Replacement Therapy

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

A Monte Carlo Simulation Approach for Beta‐Lactam Dosing in Critically Ill Patients Receiving Prolonged Intermittent Renal Replacement Therapy

Contact Info

Product

Resources

About