Pharmacokinetic/Pharmacodynamic Modeling of Antibiotics
Hartmut Derendorf, Günther Hochhaus in Handbook of Pharmacokinetic/Pharmacodynamic Correlation, 2019
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.
Economics of ESRD in Developing Countries: India
Meguid El Nahas in Kidney Diseases in the Developing World and Ethnic Minorities, 2005
Similarly, despite the universal use of newer biocompatible membranes in the rest of the world, membranes made of cuprophane are used in a vast majority of units in the developing world, especially in the government-funded hospitals. Dialyzer reuse is widespread and helps bring down the costs. The number of reuses is higher in private units with intent to increase the profits. Dialyzers are usually reprocessed manually, and the level of contaminants or the fiber bundle volume is rarely measured. This results in delivery of inadequate dialysis, frequent occurrence of pyrogenic reactions, and even sepsis following dialysis. In some countries like China and Egypt reuse is prohibited by law, whereas countries like Togo and Benin do not reuse dialyzers because of poor facilities (35).
Ertapenem
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 in Kucers’ The Use of Antibiotics, 2017
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).
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.
Extracorporeal elimination of butalbital in acute aspirin–butalbital–caffeine–codeine (Fiorinal with Codeine) poisoning
Published in Clinical Toxicology, 2018
Janelle O. Poyant, Robert Albright, Jeremy Clain, Govind Pandompatam, Erin F. Barreto
Given the pharmacokinetic profile of butalbital and the parallel concerns for salicylate intoxication, the nephrology team was consulted to consider extracorporeal clearance of the offending agents. The patient underwent a single four-hour session of intermittent hemodialysis using blood and dialysate flow rates of 350 and 600 mL/min, respectively, with a high flux, high-efficiency REVACLEAR dialyzer (Baxter International Inc., Deerfield, IL) without any adverse effects. Following approximately 35-minutes of dialysis, she acutely regained consciousness and became fully interactive with the care team. Serum and effluent concentrations measured throughout the dialysis run (Gas chromatography with mass spectrometry; Mayo Medical Laboratories, Rochester, MN), demonstrated that extracorporeal removal of butalbital was a probable contributor to this dramatic clinical improvement (Table 1). She was successfully transferred to the ward shortly thereafter and dismissed to an inpatient psychiatric facility on hospital day 6.
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).
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