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Pharmacokinetic/Pharmacodynamic Modeling of Antibiotics
Published in Hartmut Derendorf, Günther Hochhaus, Handbook of Pharmacokinetic/Pharmacodynamic Correlation, 2019
Arno Nolting, Hartmut Derendorf
Due to the innate disadvantages of dilution models, other approaches were developed based on dialysis or diffusion. In these models, the only driving force for drug exchange is the concentration gradient across the membrane or dialyzer. Reeves27 used a dialyzer apparatus to investigate the activity of ciprofloxacin against E. coli and Serratia marcescens in a two-compartment body model. In brief, the model consisted of two flasks representing the central and peripheral compartments. The central compartments contained the antibiotic. Sterile broth solution was pumped continuously into the central compartment at a flow rate appropriate to simulate a 3-h half-life. The dialyzer was of the hollow-fiber type. The effective area for drug exchange was reported as 1.1 m2. As can be seen in Figure 9, the viable count fell rapidly by two orders of magnitude, increased with decreasing ciprofloxacin concentration, only to fall to a similar degree as before when a new dose of ciprofloxacin was introduced.
Ertapenem
Published in M. Lindsay Grayson, Sara E. Cosgrove, Suzanne M. Crowe, M. Lindsay Grayson, William Hope, James S. McCarthy, John Mills, Johan W. Mouton, David L. Paterson, Kucers’ The Use of Antibiotics, 2017
Pilar Retamar, Luis-Eduardo López-Cortés
Extended daily dialysis (EDD) is an increasingly popular mode of renal-replacement therapy in critically ill patients because it combines the advantages of intermittent hemo-dialysis (IHD) and continuous renal replacement therapy (CRRT)—that is, excellent detoxification accompanied by cardiovascular tolerability. In a single-center, prospective, open-label study six ICU patients with acute renal failure undergoing EDD were treated with 1 g ertapenem given as a single intravenous dose. Blood and dialysate flow were 160 ml/minute and the length of treatment was 480 minutes. Plasma samples were collected at different time points up to 24 hours after the medication. After a single dose of 1000 mg free ertapenem, protein-unbound plasma concentrations exceeded an MIC90 value of 2 μg/ml for > 20 hours after dosing. The clearance of the tested dialyzer was 38.5 ± 14.2 ml/minute. In a recent published study of critically ill patients undergoing continuous venovenous hemodialysis (CVVHD) or continuous venovenous hemodiafiltration (CVVHDF), Monte Carlos simulations were carried out to test the ability of several ertapenem dosing regimens (500 mg/day, 750 mg/day, 500 mg/12 hours, and 1000 mg/day) to obtain effective unbound serum concentrations above 0.5, 1, and 2 μg/ml. All regimens produced unbound ertapenem concentrations above 2 μg/ml for 40% of the dosing interval for at least 96% of simulated patients (Eyler et al, 2014).
Spinning of Dialysis Grade Membranes
Published in Sirshendu De, Anirban Roy, Hemodialysis Membranes, 2017
In the present work, experiments were conducted in purely the diffusion-governed mode. In addition, the concentration gradient, that is, the driving force across the membrane decreases with time as both the feed and the dialysate are recycled. Therefore, the dialyzer in this work performs poorly compared to the continuous supply of fresh dialysate in actual dialysis. However, even in this mode of operation, the dialyzer with low-cost spinning technology is able to reduce the level of uremic toxins to the desired limit in adequate time.
Flow balance optimization and fluid removal accuracy with the Quanta SC+ hemodialysis system
Published in Expert Review of Medical Devices, 2020
Clive Buckberry, Nicholas Hoenich, Paul Komenda, Mark Wallace, John E Milad
Hemodialysis involves the use of an artificial semi-permeable membrane contained in an artificial kidney known as a dialyzer. During treatment, blood is removed from the patient via an extracorporeal circuit and is passed through the dialyzer before being returned to the patient. Blood flows through the dialyzer and is in contact with the inner surface of the membrane. The outer surface of the membrane is bathed by a continuously flowing fluid (dialysis fluid) made from a precise mixture of electrolytes and purified water. Abnormal patient biochemistry is normalized primarily by diffusion of accumulated uremic toxins into the dialysis fluid, while the fluid gained by the patient between treatments, due to an inability to pass sufficient amounts of urine to achieve homeostasis, is removed by a hydrostatic pressure gradient across the dialyzer membrane, a process referred to as ultrafiltration.
Development of liposome as a novel adsorbent for artificial liver support system in liver failure
Published in Journal of Liposome Research, 2020
Yue Shen, Yifeng Wang, Yuanyuan Shi, Huajun Tian, Qiuyu Zhu, Feng Ding
All the reagents, unless otherwise indicated, were purchased from Sigma Chemical Co. (St. Louis, MO). Amicon® Ultra Centrifugal Filters (10.0 KDa molecular weight cut-off, MWCO) were purchased from Millipore Co. (Billerica, MA). Single-Use Rapid Equilibrium Dialysis (RED) Plates (12.0 KDa MWCO) were purchased from Thermo Fisher Scientific Inc. (Rockford, IL). Bovine serum albumin (BSA) of low fatty acid was used in batch study. Bile salts were composed of cholic acid sodium (50%) and deoxycholic acid sodium (50%). High-performance liquid chromatography (HPLC) grade methanol and acetonitrile were purchased from Sinopharm Chemical Reagent Company (Shanghai, SH, China). The experimental setup for the in vitro and the in vivo circulation systems consisted of miniature peristaltic pumps (VWR International, TX), sterilized silicone dialysis tubing and a miniaturized polysulphone dialyzer specially developed for small animals (Table S1). The parameters of mini dialyzer and the hemodialysis setup has been previously described (Shi et al. 2018).
Dialysis-specific factors and incident atrial fibrillation in hemodialysis patients
Published in Renal Failure, 2020
Seung Don Baek, Soomin Jeung, Jae-Young Kang, Ki Hyun Jeon
Baseline demographic and clinical data were obtained, including age, gender, body mass index, dialysis vintage, comorbidity, vascular access type, location, and pre-dialysis blood pressure and heart rate. Dialysis prescription-related factors were the following: membrane permeability (high flux versus low flux), session frequency (thrice weekly versus twice weekly), time length per session (4 versus 3.5 h), dialyzer size (effective surface area of 1.8 m2 versus surface area of 1.4 m2), ultrafiltration rate (mL/kg/h), blood flow rate (mL/min), and dialysate calcium concentration (3 versus 2.5 mEq/L). High-flux dialyzer was defined as KUF (coefficient of ultrafiltration) >15 mL/mmHg or β2 microglobulin clearance >20 mL/min. Single-pool Kt/V and normalized protein catabolic rate were estimated every 3 months [7,8]. The ultrafiltration volume (pre-dialysis body weight – post-dialysis body weight) was summated over the first month after enrollment, and the mean ultrafiltration rate (mL/kg/h, ultrafiltration volume divided by the dialysis time length and dry body weight) was calculated. All variables were recorded at the time of enrollment.