Elimination of piperacillin and tazobactam by renal replacement therapies with AN69 and polysulfone hemofilters: evaluation of the sieving coefficient.
ABSTRACT 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.
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.
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.
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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ABSTRACT: The multiple organ dysfunction syndrome (MODS) is characterized by more than one organ system failing, especially during critically illness. MODS is the leading cause of morbidity and mortality in current ICU practice; moreover, multiple organ dysfunction, especially liver and kidneys, may significantly affect the pharmacokinetics (PKs) of different drugs that are currently administered in critically ill patients. These PKs alterations may either result in insufficient drug concentrations to achieve the desired effects or in blood and tissue accumulation, with the development of serious adverse events. The use of extra-corporeal circuits, such as extracorporeal membrane oxygenation (ECMO) and continuous renal replacement therapy (CRRT), may further contribute to PKs changes in this patients' population. In this review, we have described the main PK changes occurring in all these conditions and how drug concentrations may potentially be affected. The lack of prospective studies on large cohorts of patients makes impossible any specific recommendation on drug regimen adjustment in ICU patients. Nevertheless, the clinicians should be aware of these abnormalities in order to better understand some unexpected therapeutic issues occurring in such patients.Advanced drug delivery reviews. 05/2014;
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ABSTRACT: Clinicians commonly rely on tertiary drug information references to guide drug dosages for patients who are receiving continuous renal replacement therapy (CRRT). It is unknown whether the dosage recommendations in these frequently used references reflect the most current evidence. To determine the presence and accuracy of drug dosage recommendations for patients undergoing CRRT in 4 drug information references. Medications commonly prescribed during CRRT were identified from an institutional medication inventory database, and evidence-based dosage recommendations for this setting were developed from the primary and secondary literature. The American Hospital Formulary System-Drug Information (AHFS-DI), Micromedex 2.0 (specifically the DRUGDEX and Martindale databases), and the 5th edition of Drug Prescribing in Renal Failure (DPRF5) were assessed for the presence of drug dosage recommendations in the CRRT setting. The dosage recommendations in these tertiary references were compared with the recommendations derived from the primary and secondary literature to determine concordance. Evidence-based drug dosage recommendations were developed for 33 medications administered in patients undergoing CRRT. The AHFS-DI provided no dosage recommendations specific to CRRT, whereas the DPRF5 provided recommendations for 27 (82%) of the medications and the Micromedex 2.0 application for 20 (61%) (13 [39%] in the DRUGDEX database and 16 [48%] in the Martindale database, with 9 medications covered by both). The dosage recommendations were in concordance with evidence-based recommendations for 12 (92%) of the 13 medications in the DRUGDEX database, 26 (96%) of the 27 in the DPRF5, and all 16 (100%) of those in the Martindale database. One prominent tertiary drug information resource provided no drug dosage recommendations for patients undergoing CRRT. However, 2 of the databases in an Internet-based medical information application and the latest edition of a renal specialty drug information resource provided recommendations for a majority of the medications investigated. Most dosage recommendations were similar to those derived from the primary and secondary literature. The most recent edition of the DPRF is the preferred source of information when prescribing dosage regimens for patients receiving CRRT.The Canadian journal of hospital pharmacy 05/2012; 65(3):188-95.
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ABSTRACT: To evaluate the pharmacokinetics of piperacillin/tazobactam in critically ill patients undergoing continuous renal replacement therapy (CRRT) and to assess the success of the therapy against susceptible bacteria. Sixteen patients undergoing CRRT with different degrees of renal function were included in the study. Blood and ultrafiltrate samples were drawn after administration of piperacillin/tazobactam (4/0.5 g) every 4, 6 or 8 h. The data were analysed by a population approach using NONMEM 7.2. The probability of target attainment (PTA) of maintaining free piperacillin levels above the MIC during the entire dosing interval was estimated by simulation of intermittent and continuous infusions. The pharmacokinetics of piperacillin and tazobactam were best described by two-compartment models where the elimination of both drugs was conditioned by renal [dependent on creatinine clearance (CLCR)], non-renal and extracorporeal clearances. A 20 min infusion of piperacillin/tazobactam administered every 6 h provided high PTAs against MICs ≤32 mg/L in patients with severe renal failure. In patients with normal or moderate renal function PTAs ≥90% were only obtained up to MICs ≤8 mg/L with short infusions. However, simulating continuous infusion, higher probabilities of success were obtained against MICs of 32 and 16 mg/L when CLCR was 50 and 100 mL/min, respectively. Population pharmacokinetic models have been developed and validated for piperacillin and tazobactam. Based on the pharmacokinetic/pharmacodynamic analysis, dosing recommendations are given considering the residual renal function of the patient and the MIC for the isolated bacteria.Journal of Antimicrobial Chemotherapy 08/2013; · 5.34 Impact Factor