scholarly journals Proposal of a Pharmacokinetically Optimized Dosage Regimen of Antibiotics in Patients Receiving Continuous Hemodiafiltration

2011 ◽  
Vol 55 (12) ◽  
pp. 5804-5812 ◽  
Author(s):  
Takehito Yamamoto ◽  
Nobuhiro Yasuno ◽  
Shoichi Katada ◽  
Akihiro Hisaka ◽  
Norio Hanafusa ◽  
...  
Keyword(s):  
Critically Ill ◽  
Critically Ill Patients ◽  
Drug Clearance ◽  
Minor Effect ◽  
Optimal Dosage ◽  
Continuous Hemodiafiltration ◽  
Unbound Fraction ◽  
Artificial Plasma

ABSTRACTThe aim of the study was to quantitatively predict the clearance of three antibiotics, amikacin, vancomycin, and teicoplanin, during continuous hemodiafiltration (CHDF) and to propose their optimal dosage in patients receiving CHDF. For this goal,in vitroCHDF experiments with a polyacrylonitrile (PAN) membrane were first performed using these antibiotics, and then the clearances were compared within vivoCHDF situations determined in 16 critically ill patients. Thein vitroCHDF clearances were described as the product of the outflow rate of a drain (Qoutflow) and the drug unbound fraction in artificial plasma, indicating that drug adsorption to the PAN membrane has minor effect on drug clearance in our settings. The observedin vivoclearances also agreed very well with the predicted values, with a product ofQoutflowand plasma unbound fraction, when residual creatinine clearance (CLCR) was taken into account (within a range of 0.67- to 1.5-fold for 15 of 16 patients). Based on these results, a nomogram of the optimized dosages of amikacin, vancomycin, and teicoplanin was proposed, and it was evident thatQoutflowand residual CLCRare major determinants of the dosage and dosing interval for these antibiotics. Although the applicability needs to be confirmed with another type of membrane or higherQoutflow, our nomogram can help determine the dosage setting in critically ill patients receiving CHDF.

Studies on Metabolism of Urokinase and Mechanism of Thrombolysis by Urokinase

1979 ◽  
Vol 42 (03) ◽  
pp. 885-894 ◽  
Author(s):  
Tatsuo Ueno ◽  
Norio Kobayashi ◽  
Tadashi Maekawa
Keyword(s):  
Molecular Weight ◽  
Plasma Clearance ◽  
Radioactive Material ◽  
Optimal Dosage ◽  
Plasma Clot ◽  
Optimal Dosage Regimen ◽  
Arterial Thrombus ◽  
Contact Experiment

SummaryPharmacokinetics of intravenously injected 125I-labeled urokinase (125I-UK) of a molecular weight of 33,000 daltons in normal rabbits and patients with various diseases were investigated. The plasma clearance of 125I-UK in rabbits was described by a biexponential curve within six hours with a half-life of 8 minutes, 2.3 hours, respectively. The radioactivity in the liver and kidneys 15 minutes after iv injection with 125I-UK was 9.6% and 14.0% of the radioactivity injected, respectively. Approximately 80% of the total radioactive material injected was excreted in the urine in 18 hours. No increase in activator activity in the urine was observed after a large amount of UK injection. Activity uptake of 125I-UK by experimentally induced arterial thrombus was little. Lysis of the stasis thrombus was produced by injecting 7.5 × 104 IU of UK in only one out of 8 rabbits. In vitro contact experiment revealed that transfer of 125I-UK to plasma clot is slow (24 hours for 10% of 125I-UK by plasma clot). In 4 patients plasma clearance of 125I-UK was essentially similar to that in rabbits. From the results obtained optimal dosage regimen of UK administration for complete thrombolysis in vivo was discussed.

scholarly journals Promising potential of [177Lu]Lu-DOTA-folate to enhance tumor response to immunotherapy—a preclinical study using a syngeneic breast cancer model

2020 ◽  
Author(s):  
Patrycja Guzik ◽  
Klaudia Siwowska ◽  
Hsin-Yu Fang ◽  
Susan Cohrs ◽  
Peter Bernhardt ◽  
...  
Keyword(s):  
Tumor Growth ◽  
Survival Time ◽  
Tumor Cells ◽  
Median Survival ◽  
Breast Tumor ◽  
Median Survival Time ◽  
Therapy Outcome ◽  
Minor Effect

Abstract Purpose It was previously demonstrated that radiation effects can enhance the therapy outcome of immune checkpoint inhibitors. In this study, a syngeneic breast tumor mouse model was used to investigate the effect of [177Lu]Lu-DOTA-folate as an immune stimulus to enhance anti-CTLA-4 immunotherapy. Methods In vitro and in vivo studies were performed to characterize NF9006 breast tumor cells with regard to folate receptor (FR) expression and the possibility of tumor targeting using [177Lu]Lu-DOTA-folate. A preclinical therapy study was performed over 70 days with NF9006 tumor-bearing mice that received vehicle only (group A); [177Lu]Lu-DOTA-folate (5 MBq; 3.5 Gy absorbed tumor dose; group B); anti-CTLA-4 antibody (3 × 200 μg; group C), or both agents (group D). The mice were monitored regarding tumor growth over time and signs indicating adverse events of the treatment. Results [177Lu]Lu-DOTA-folate bound specifically to NF9006 tumor cells and tissue in vitro and accumulated in NF9006 tumors in vivo. The treatment with [177Lu]Lu-DOTA-folate or an anti-CTLA-4 antibody had only a minor effect on NF9006 tumor growth and did not substantially increase the median survival time of mice (23 day and 19 days, respectively) as compared with untreated controls (12 days). [177Lu]Lu-DOTA-folate sensitized, however, the tumors to anti-CTLA-4 immunotherapy, which became obvious by reduced tumor growth and, hence, a significantly improved median survival time of mice (> 70 days). No obvious signs of adverse effects were observed in treated mice as compared with untreated controls. Conclusion Application of [177Lu]Lu-DOTA-folate had a positive effect on the therapy outcome of anti-CTLA-4 immunotherapy. The results of this study may open new perspectives for future clinical translation of folate radioconjugates.

scholarly journals Pharmacokinetics and the optimal regimen for levofloxacin in critically ill patients receiving continuous hemodiafiltration

2015 ◽  
Vol 3 (1) ◽  
Author(s):  
Takeshi Wada ◽  
Masaki Kobayashi ◽  
Yuichi Ono ◽  
Asumi Mizugaki ◽  
Kenichi Katabami ◽  
...  
Keyword(s):  
Critically Ill ◽  
Critically Ill Patients ◽  
Continuous Hemodiafiltration ◽  
Optimal Regimen

Evaluation of plasma levels of meropenem in septic patients during extracorporeal blood purification

2021 ◽  
Vol 20 (4) ◽  
pp. 81-94
Author(s):  
Artem V. Marukhov ◽  
Elena V. Murzina ◽  
Mikhail V. Zakharov ◽  
Genrikh A. Sofronov ◽  
Lyudmila V. Buryakova ◽  
...  
Keyword(s):  
Septic Shock ◽  
Critically Ill ◽  
Critically Ill Patients ◽  
Selective Adsorption ◽  
Plasma Concentrations ◽  
Blood Purification ◽  
Continuous Hemodiafiltration ◽  
Extracorporeal Blood ◽  
Extracorporeal Blood Purification ◽  
Extracorporeal Support

The relevance. Meropenem is a broad-spectrum carbapenem antibiotic widely used to treat patients with sepsis / septic shock. Critically ill patients are usually supported with one of the forms extracorporeal blood purification. However, data on the effect of various extracorporeal support techniques on the pharmacokinetics and pharmacodynamics of meropenem are insufficient or contradictory. Aim: To evaluate the effectiveness of meropenem dosage regimens in the treatment of septic patients during extracorporeal blood purification. Materials and methods. Plasma concentrations of meropenem were monitored in three critically ill patients with sepsis or septic shock. Patients were treated using various extracorporeal support techniques. Meropenem was used as empirical antibacterial mono- or complex therapy (1 g every 8 or 12 hours). Meropenem concentrations in plasma were determined by validated assay methods on Acquity ultraefficient liquid chromatography (UPLC) H-Class system. Results. It is shown that the meropenem plasma concentration in critically ill patients changes significantly. It was found that the standard meropenem dosing regimens in patients with sepsis / septic shock during continuous hemodiafiltration do not ensure the achievement of the PK/PD target of 100% TMIC for sensitive strains (MIC2 mg/L) and for intermediate resistance pathogens (2MIC8 mg/L). Continuous hemofiltration and selective adsorption of lipopolysaccharide have a less pronounced effect on the clearance of meropenem. Conclusion. To increase the effectiveness of antibacterial therapy, it is necessary to conduct research aimed at developing protocols for dosing antibacterial drugs for the treatment of sepsis during extracorporeal blood purification.

In vivo Elimination of Clonidine by Continuous Venovenous Hemofiltration in Critically Ill Patients

2020 ◽  
Vol 49 (5) ◽  
pp. 622-626
Author(s):  
Huub L.A. van den Oever ◽  
Marieke Zeeman ◽  
Polina Nassikovker ◽  
Carmen Bles ◽  
Fred A.L. van Steveninck ◽  
...  
Keyword(s):  
Intensive Care Unit ◽  
Intensive Care ◽  
Critically Ill ◽  
Critically Ill Patients ◽  
Continuous Venovenous Hemofiltration ◽  
Kidney Dysfunction ◽  
Sieving Coefficient ◽  
The Mean ◽  
Ventilated Patients

Background: Clonidine is an α2-agonist that is commonly used for sedation in the intensive care unit. When patients are on continuous venovenous hemofiltration (CVVH) in the presence of kidney dysfunction, the sieving coefficient of clonidine is required to estimate how much drug is removed by CVVH. In the present study, we measured the sieving coefficient of clonidine in critically ill, ventilated patients receiving CVVH. Methods: A total of 20 samples of plasma and ultrafiltrate of 3 patients on CVVH, using a standard 1.5 m2 polyacrylonitrile AN69 membrane, during continuous clonidine infusion were collected. After correction for the effect of predilution, we calculated the sieving coefficient for clonidine. Results: The mean sieving coefficient of clonidine was 0.52 (SD 0.097). Conclusion: Using a polyacrylonitrile AN69 membrane in a CVVH machine, the in vivo sieving coefficient of clonidine was 0.52.

Critical-care medicine and the acute-care laboratory

1990 ◽  
Vol 36 (8) ◽  
pp. 1552-1556 ◽  
Author(s):  
J R Hall
Keyword(s):  
Critical Care ◽  
Data Management ◽  
Critically Ill ◽  
Critically Ill Patients ◽  
Ex Vivo ◽  
Hospital Costs ◽  
Cost Effective ◽  
Critical Care Medicine ◽  
Time Utilization

Abstract Critical-care medicine today is practiced by anesthesiologists, internists, pediatricians, and surgeons. Outcome from today's management of critically ill patients is very good, yet associated costs are very high. Over one-half of the hospital costs of critically ill patients emanates from the intensive-care unit (ICU), although the ICU stay accounts for less than 20% of their time in the hospital. Outside of the operating room, the ICU is the most expensive location for patient care in the hospital, and laboratory tests are the most expensive single item. Plans for cost containment should incorporate the following: more effective data management, education of practitioners about appropriateness and costs of tests, conversion from laboratory measurements to appropriate in vivo and ex vivo measurements, and real-time utilization assessment. To provide high-quality, cost-effective critical care in the future, laboratorians and clinicians must work together today to meet the challenges of technology, data management, and staff education.

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