Pharmacokinetics of ertapenem in critically ill patients with acute renal failure undergoing extended daily dialysis

Burkhardt, Olaf; Hafer, Carsten; Langhoff, Anita; Kaever, Volkhard; Kumar, Vipul; Welte, Tobias; Haller, Hermann; Fliser, Danilo; Kielstein, Jan T.

doi:10.1093/ndt/gfn472

Cited by 58 publications

(52 citation statements)

References 16 publications

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“…Mean volume in the peritoneal space was 2.6 L, roughly the amount of fluid administered during each exchange. Clearance was approximately 0.3 L/h, close to previous approximations for patients with minimal kidney function (8,(23)(24)(25). Finally, a physiologic amount of residual drug (approximately 0.5 mg) was estimated to remain in the peritoneal cavity after drainage.…”

Section: Discussionsupporting

confidence: 76%

“…Intraperitoneal (IP) administration of daptomycin is a possible alternative to IV administration (27)(28)(29). However, further pharmacokinetic, clinical, and stability studies are necessary before IP administration of daptomycin is adopted as the standard of practice for peritonitis (8). Several things should be noted when interpreting these results.…”

Section: Discussionmentioning

confidence: 99%

“…A relatively recent addition to the armamentarium against MRSA is daptomycin. Daptomcyin is a lipopeptide antibiotic currently indicated for complicated skin and soft tissue infections and bloodstream infections due to S. aureus including MRSA (8,9). Although the pharmacokinetics (PK) of daptomycin are well described in the general population (primarily renally eliminated, half-life of approximately 8 h, volume of distribution of approximately 0.1 L/kg, and approximately 90 to 93% protein bound), limited information exists regarding the pharmacokinetics and optimal dosing of daptomycin in patients on PD (10,11).…”

Section: Introductionmentioning

confidence: 99%

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Pharmacokinetics and Pharmacodynamics of Intravenous Daptomycin during Continuous Ambulatory Peritoneal Dialysis

Cardone

Lodise²,

Patel³

et al. 2011

Clinical Journal of the American Society of Nephrology

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Summary Background and objectives This study sought to (1) characterize the pharmacokinetic (PK) profile of intravenous (IV) daptomycin among patients receiving continuous ambulatory peritoneal dialysis (CAPD); (2) identify optimal IV CAPD dosing schemes; and (3) determine extent of daptomycin penetration into the peritoneal space after IV administration. Design, setting, participants, & measurements A PK study was conducted among eight CAPD patients. Population PK modeling and Monte Carlo simulation (MCS) were used to identify CAPD dosing schemes providing efficacy and toxicity plasma profiles comparable with those obtained from MCS using the daptomycin population PK model derived from patients in the Staphylococcus aureus bacteremia-infective endocarditis (SAB-IE) study. The primary efficacy exposure target was the area under the curve (AUC). For toxicity, the goal was to identify CAPD dosing schemes that minimized plasma trough concentrations in excess of 24.3 mg/L. Finally, peritoneal cavity penetration was determined. Results Administration of IV daptomycin 4 or 6 mg/kg, depending on indication, every 48 h was identified as the optimal CAPD dosing scheme. This regimen provided cumulative (AUC0–48) and daily partitioned (AUC0–24h and AUC24–48h) plasma AUC values similar to the SAB-IE or “typical patient” simulations. In addition, the proportion of patients likely to experience an elevated trough concentration in excess of 24.3 mg/L was similar between every 48 h CAPD dosing and the referent group. Penetration into the peritoneal cavity was 6% of plasma. Conclusions Daptomycin 4 or 6 mg/kg, on the basis of indication, IV every 48 h was found to be the optimal IV CAPD dosing scheme.

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Section: Discussionsupporting

confidence: 76%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Pharmacokinetics and Pharmacodynamics of Intravenous Daptomycin during Continuous Ambulatory Peritoneal Dialysis

Cardone

Lodise²,

Patel³

et al. 2011

Clinical Journal of the American Society of Nephrology

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“…In some instances, critically ill patients requiring RRTs require higher doses of antibiotic than recommended for individuals receiving intermittent hemodialysis for end-stage renal disease (13,23,24). A pharmacokinetic study of ertapenem in critically ill subjects requiring extended daily dialysis (blood and dialysate flow rates of 160 ml/min, treatment duration of 480 min) suggested that a dose of 1 g every 24 h, substantially higher than the manufacturer's suggested dosing for patients with creatinine clearance of Ͻ30 ml/min/1.73 m 2 (500 mg q24h) or receiving maintenance hemodialysis (500 mg within 6 h prior to hemodialysis, supplementary 150 mg following the hemodialysis session), is more appropriate to achieve bactericidal targets (1,25).…”

Section: Discussionmentioning

confidence: 99%

Pharmacokinetics of Ertapenem in Critically Ill Patients Receiving Continuous Venovenous Hemodialysis or Hemodiafiltration

Eyler

Vilay

Nader

et al. 2014

Antimicrob Agents Chemother

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jThis study characterizes the pharmacokinetics of ertapenem, a carbapenem antibiotic, in critically ill adult subjects receiving continuous renal replacement therapy (CRRT). Eight critically ill patients with suspected/known Gram-negative infections receiving continuous venovenous hemodialysis (CVVHD) or continuous venovenous hemodiafiltration (CVVHDF) and ertapenem were enrolled. One gram of ertapenem was infused over 30 min. Predialyzer blood samples were drawn with the first dose of ertapenem from the hemodialysis tubing at time zero, 30 min, and 1, 2, 4, 8, 12, 18, and 24 h after the start of the ertapenem infusion. Effluent was collected at the same time points. Ertapenem total serum, unbound serum, and effluent concentrations from all eight subjects were used simultaneously to perform a population compartmental pharmacokinetic modeling procedure using NONMEM. Monte Carlo simulations were performed to evaluate the ability of several ertapenem dosing regimens (500 mg once daily, 750 mg once daily, 500 mg twice daily, and 1,000 mg once daily) to obtain effective unbound serum concentrations above 0.5, 1, and 2 g/ml. For our simulated patients, all regimens produced unbound ertapenem concentrations above 2 g/ml for 40% of the dosing interval for at least 96% of simulated patients. (This study has been registered at ClinicalTrials.gov under registration no. NCT00877370.)

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“…While ertapenem pharmacokinetic (PK) parameters are well described in the general population, there are scant data on the PK properties of ertapenem in patients receiving renal replacement therapies (4,20). To date, there are no published studies evaluating the PK of ertapenem during PD, a dialysis modality used by 26,000 patients in the United States (27).…”

mentioning

confidence: 99%

Ertapenem Pharmacokinetics and Pharmacodynamics during Continuous Ambulatory Peritoneal Dialysis

Cardone

Grabe

Kulawy

et al. 2012

Antimicrob Agents Chemother

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Scant data exist for the pharmacokinetics (PK) of ertapenem in patients on continuous ambulatory peritoneal dialysis (CAPD).The goals of this study were to characterize the PK profile of ertapenem during CAPD, determine the extent of ertapenem penetration into the peritoneal cavity, and quantify the probability of the target attainment (PTA) profile in the serum and peritoneal cavity. A single-dose PK study was conducted in seven patients on CAPD. Population PK modeling and Monte Carlo simulation determined the probability that ertapenem at 500 mg intravenously (i.v.) every 24 h (q24h) would achieve concentrations in excess of the MIC for 40% of the dosing interval (40% T>MIC, where T is time) in the serum and peritoneal cavity. Monte Carlo simulation was also used to calculate the peritoneal cavity/serum mean and median penetration ratios by estimating the area under the concentration-time curve in the peritoneal cavity and serum (AUC Peritoneal and AUC Serum , respectively) from zero to infinity after a single simulated dose

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Pharmacokinetics of ertapenem in critically ill patients with acute renal failure undergoing extended daily dialysis

Abstract: In contrast to patients undergoing regular IHD, in which a dose reduction is required, our data suggest that in patients treated with EDD a standard dose of ertapenem (1 g/day), i.e. dose for patients without renal failure, is required to maintain adequate plasma drug levels.

Cited by 58 publications

References 16 publications

Pharmacokinetics and Pharmacodynamics of Intravenous Daptomycin during Continuous Ambulatory Peritoneal Dialysis

Pharmacokinetics and Pharmacodynamics of Intravenous Daptomycin during Continuous Ambulatory Peritoneal Dialysis

Pharmacokinetics of Ertapenem in Critically Ill Patients Receiving Continuous Venovenous Hemodialysis or Hemodiafiltration

Ertapenem Pharmacokinetics and Pharmacodynamics during Continuous Ambulatory Peritoneal Dialysis

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