Single-dose pharmacokinetics of ofloxacin during continuous venovenous hemofiltration in critical care patients

Fuhrmann, Valentin; Schenk, Peter; Mittermayer, C.; Menyawi, Ibrahim El; Ratheiser, Klaus; Thalhammer, Florian

doi:10.1016/s0272-6386(03)00656-5

Cited by 10 publications

(4 citation statements)

References 24 publications

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“…During CVVH, Fuhrmann et al found a mean serum ofloxacin concentration peak of 5.5 ± 0.7 mg/L and a t1/2, hemofiltration clearance, and total removal of 2.8 ± 0.5 h, 89.9 ± 4.5 mL/min, and 76.9% ± 7.1%, respectively. [40] In our study, mean ofloxacin SC, CL CVVH and t1/2 ranged from 59.50 to 66.00%; 18.74 to 52.19 mL/min and 6.58 to 8.72 h, respectively. However, due to the high volume of distribution, serum concentration is comparable between the standard and high volume group, implying that no dose adaptation is required at increasing CVVH dose.…”

Section: Ofloxacinsupporting

confidence: 43%

Pharmacokinetics and pharmacodynamics of anti-infective agents during continuous veno-venous hemofiltration in critically ill patients: Lessons learned from an ancillary study of the IVOIRE trial

Breilh

Honoré

Bels

et al. 2019

Journal of Translational Internal Medicine

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Background: Hemofiltration rate, changes in blood and ultrafiltration flow, and discrepancies between the prescribed and administered doses strongly influence pharmacokinetics (PK) and pharmacodynamics (PD) of antimicrobial agents during continuous veno-venous hemofiltration (CVVH) in critically ill patients. Methods: Ancillary data were from the prospective multicenter IVOIRE (hIgh VOlume in Intensive caRE) study. High volume (HV, 70 mL/kg/h) was at random compared with standard volume (SV, 35 mL/kg/h) CVVH in septic shock patients with acute kidney injury (AKI). PK/PD parameters for all antimicrobial agents used in each patient were studied during five days. Results: Antimicrobial treatment met efficacy targets for both percentage of time above the minimal inhibitory concentration and inhibitory quotient. A significant correlation was observed between the ultrafiltration flow and total systemic clearance (Spearman test: P < 0.005) and between CVVH clearance and drug elimination half-life (Spearman test: P < 0.005). All agents were easily filtered. Mean sieving coefficient ranged from 38.7% to 96.7%. Mean elimination half-life of all agents was significantly shorter during HV-CVVH (from 1.29 to 28.54 h) than during SV-CVVH (from 1.51 to 33.85 h) (P < 0.05). Conclusions:This study confirms that CVVH influences the PK/PD behavior of most antimicrobial agents. Antimicrobial elimination was directly correlated with convection rate. Current antimicrobial dose recommendations will expose patients to underdosing and increase the risk for treatment failure and development of resistance. Dose recommendations are proposed for some major antibiotic and antifungal treatments in patients receiving at least 25 mL/kg/h CVVH.

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Section: Ofloxacinsupporting

confidence: 43%

Pharmacokinetics and pharmacodynamics of anti-infective agents during continuous veno-venous hemofiltration in critically ill patients: Lessons learned from an ancillary study of the IVOIRE trial

Breilh

Honoré

Bels

et al. 2019

Journal of Translational Internal Medicine

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“…This small discrepancy might be explained by the fact that the bovine blood used in this ex vivo study has low albumin concentrations (mean concentration of 3.0-3.3 g/dL) [12] or perhaps these agents do not bind as avidly to bovine albumin as they do to human albumin. Previous in vitro and in vivo studies have reported similar discrepancies between observed and predicted pharmacokinetic parameters for antibiotics [16, 30, 31, 32, 33, 34]. The discrepancy in SA/SC likely has little clinical significance, as nearly 40% of critically ill patients are hypoalbuminemic (<2.5 g/dL) [35,] which results in decreased protein binding and increased free drug concentrations.…”

Section: Discussionmentioning

confidence: 83%

Ex vivo Ceftolozane/Tazobactam Clearance during Continuous Renal Replacement Therapy

et al. 2017

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Background/Aims: To determine ceftolozane/tazobactam transmembrane clearances (CL_TM) in continuous hemofiltration (CHF) and continuous hemodialysis (CHD) and to determine optimal ceftolozane/tazobactam dosing regimens for patients receiving continuous renal replacement therapy (CRRT). Method: Validated, ex vivo CHF and CHD bovine blood models using polysulfone (HF1400) and AN69 (Multiflow 150-M) hemofilters were used to evaluate adsorption and CL_TM at different effluent flow rates. Monte Carlo simulations (MCS) using pharmacokinetic parameters from published studies and CL_TM from this study were used to generate ceftolozane/tazobactam dosing for patients receiving CRRT. Results: CHF and CHD CL_TM did not differ at equivalent effluent rates. CL_TM approximated effluent flow rates. No adsorption of ceftolozane/tazobactam occurred for either hemofilter. Effluent flow was the most important determinant of MCS-derived doses. Conclusion: CRRT clearances of ceftolozane/tazobactam depended on effluent flow rates but not hemofilter types. MCS-derived ceftolozane/tazobactam doses of 750 (500/250)-1,500 (1,000/500) mg every 8 h met pharmacodynamic targets for virtual patients receiving CRRT at contemporary effluent rates.

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“…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: 62%

“…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] . Some authors defend that different affi nities of drugs on whole blood binding sites could be the reason of the deviation of drug sieving coeffi cients from predicted values [42] .…”

Section: Discussionmentioning

confidence: 99%

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

et al. 2006

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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.

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Single-dose pharmacokinetics of ofloxacin during continuous venovenous hemofiltration in critical care patients

Cited by 10 publications

References 24 publications

Pharmacokinetics and pharmacodynamics of anti-infective agents during continuous veno-venous hemofiltration in critically ill patients: Lessons learned from an ancillary study of the IVOIRE trial

Pharmacokinetics and pharmacodynamics of anti-infective agents during continuous veno-venous hemofiltration in critically ill patients: Lessons learned from an ancillary study of the IVOIRE trial

Ex vivo Ceftolozane/Tazobactam Clearance during Continuous Renal Replacement Therapy

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

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