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Isabel Spriet - One of the best experts on this subject based on the ideXlab platform.
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Development and External Validation of an Online Clinical Prediction Model for Augmented Renal Clearance in Adult Mixed Critically Ill Patients: The Augmented Renal Clearance Predictor.
Critical care medicine, 2020Co-Authors: Matthias Gijsen, Chao-yuan Huang, Marine Flechet, Ruth Van Daele, Peter Declercq, Yves Debaveye, Philippe Meersseman, Geert Meyfroidt, Joost Wauters, Isabel SprietAbstract:OBJECTIVES Augmented Renal Clearance might lead to subtherapeutic plasma levels of drugs with predominant Renal Clearance. Early identification of augmented Renal Clearance remains challenging for the ICU physician. We developed and validated our augmented Renal Clearance predictor, a clinical prediction model for augmented Renal Clearance on the next day during ICU stay, and made it available via an online calculator. We compared its predictive performance with that of two existing models for augmented Renal Clearance. DESIGN Multicenter retrospective registry-based cohort study. SETTING Three Belgian tertiary care academic hospitals. PATIENTS Adult medical, surgical, and cardiac surgery ICU patients. INTERVENTIONS None. MEASUREMENTS AND MAIN RESULTS Development of the prediction model was based on clinical information available during ICU stay. Out of 33,258 ICU days, we found augmented Renal Clearance on 19.6% of all ICU days in the development cohort. We retained six clinical variables in our augmented Renal Clearance predictor: day from ICU admission, age, sex, serum creatinine, trauma, and cardiac surgery. We assessed performance by measuring discrimination, calibration, and net benefit. We externally validated the final model in a single-center population (n = 10,259 ICU days). External validation confirmed good performance with an area under the curve of 0.88 (95% CI 0.87-0.88) and a sensitivity and specificity of 84.1 (95% CI 82.5-85.7) and 76.3 (95% CI 75.4-77.2) at the default threshold probability of 0.2, respectively. CONCLUSIONS Augmented Renal Clearance on the next day can be predicted with good performance during ICU stay, using routinely collected clinical information that is readily available at bedside. Our augmented Renal Clearance predictor is available at www.arcpredictor.com.
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Augmented Renal Clearance in non-critically ill abdominal and trauma surgery patients is an underestimated phenomenon: A point prevalence study.
The journal of trauma and acute care surgery, 2016Co-Authors: Peter Declercq, Joost Wauters, Stefaan Nijs, Andre Dʼhoore, Eric Van Wijngaerden, Albert Wolthuis, Anthony De Buck Van Overstraeten, Isabel SprietAbstract:BACKGROUND Augmented Renal Clearance refers to increased Renal elimination of circulating solutes as compared with normal baseline and could lead to underexposure of frequently used Renally eliminated antimicrobials. The primary objective was to assess the prevalence of augmented Renal Clearance in an adult non-critically ill surgery population. Besides, predictors for augmented Renal Clearance were investigated. A prospective observational single-center point prevalence study was conducted. METHODS The measured creatinine Clearance based on an 8-hour urinary collection was used as primary method for determining kidney function. Augmented Renal Clearance was defined as measured creatinine Clearance of 130 mL/min per 1.73m² or greater. A Poisson regression model was applied to identify predictors for augmented Renal Clearance. RESULTS Augmented Renal Clearance prevalence was 30% and 35% in 103 abdominal and 129 trauma surgery patients, respectively. Younger age (abdominal cohort: relative risk, 0.963 (95% CI, 0.949-0.978); trauma cohort: relative risk, 0.971 [95% CI, 0.960-0.983]) and also for trauma surgery patients, male sex (relative risk, 1.808 [95% CI, 1.026-3.185]) were found to be independent predictors for augmented Renal Clearance. CONCLUSIONS Augmented Renal Clearance is an underestimated phenomenon in adult non-critically ill surgery patients. Especially younger patients, and, in the subset of trauma surgery, males are prone to exhibit augmented Renal Clearance. Since augmented Renal Clearance is a risk factor for lower antimicrobial exposure, the impact of augmented Renal Clearance in relation to antimicrobial underexposure should be investigated in this population. LEVEL OF EVIDENCE Prognostic/epidemiological study, level III.
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Augmented Renal Clearance in the Critically Ill: How to Assess Kidney Function
The Annals of pharmacotherapy, 2012Co-Authors: Veerle Grootaert, Yves Debaveye, Geert Meyfroidt, Ludo Willems, Isabel SprietAbstract:BACKGROUND:Augmented Renal Clearance in critically ill patients can result in underdosing of life-saving drugs, potentially leading to therapeutic failure. To detect this phenomenon, correct assessment of the kidney function is essential. Currently, little is known about the validity of mathematical formulas to estimate Renal function in this subset of patients.OBJECTIVE:To evaluate the validity of different methods to estimate kidney function in critically ill patients with augmented Renal Clearance by comparing measured Renal Clearance with estimated Clearance using different formulas.METHODS:An observational, retrospective, single-center study was conducted in a 34-bed surgical intensive care unit (SICU) of the University Hospitals Leuven, Leuven, Belgium. Adults admitted to the SICU in 2010 with a measured creatinine Clearance (CrCl) of 120 mL/min or more (based on 24-hour urinary collection) were included. The measured Clearance values were compared with estimated Clearance values as calculated by th...
Ursula Breyer-pfaff - One of the best experts on this subject based on the ideXlab platform.
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Renal Clearance of pyridostigmine in myasthenic patients and volunteers under the influence of ranitidine and pirenzepine
Xenobiotica, 1993Co-Authors: B. Eiermann, N. Sommer, D. Winne, U. Maier, Fritz Schumm, Ursula Breyer-pfaffAbstract:1. To assess the contribution of tubular secretion to the Renal excretion of pyridostigmine, and its modification by other cationic drugs, six volunteers were given single oral doses of 60-mg pyridostigmine bromide with and without co-administration of ranitidine or pirenzepine. Renal Clearances were determined by h.p.l.c. analysis of pyridostigmine and enzymic measurement of endogenous creatinine in plasma and urine.2. In patients with myasthenia receiving continuous pyridostigmine therapy, Renal Clearance values were obtained in the same manner with and without ranitidine (10 patients) or pirenzepine (nine patients) co-medication.3. Pyridostigmine was not bound to plasma proteins. Its Renal Clearance averaged 6.65 ml/min per kg (350% of the creatinine Clearance) in all subjects, 74% being due to net tubular secretion.4. Mean values for pyridostigmine Renal Clearance and for Clearance by secretion were decreased in the presence of pirenzepine, but plasma concentrations were not affected significantly. Ra...
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Renal Clearance of pyridostigmine in myasthenic patients and volunteers under the influence of ranitidine and pirenzepine
Xenobiotica; the fate of foreign compounds in biological systems, 1993Co-Authors: B. Eiermann, N. Sommer, D. Winne, U. Maier, Fritz Schumm, Ursula Breyer-pfaffAbstract:1. To assess the contribution of tubular secretion to the Renal excretion of pyridostigmine, and its modification by other cationic drugs, six volunteers were given single oral doses of 60-mg pyridostigmine bromide with and without co-administration of ranitidine or pirenzepine. Renal Clearances were determined by h.p.l.c. analysis of pyridostigmine and enzymic measurement of endogenous creatinine in plasma and urine. 2. In patients with myasthenia receiving continuous pyridostigmine therapy, Renal Clearance values were obtained in the same manner with and without ranitidine (10 patients) or pirenzepine (nine patients) co-medication. 3. Pyridostigmine was not bound to plasma proteins. Its Renal Clearance averaged 6.65 ml/min per kg (350% of the creatinine Clearance) in all subjects, 74% being due to net tubular secretion. 4. Mean values for pyridostigmine Renal Clearance and for Clearance by secretion were decreased in the presence of pirenzepine, but plasma concentrations were not affected significantly. Ranitidine caused a small non-significant decrease of the pyridostigmine Clearance in patients. 5. Pyridostigmine had a higher elimination (2 h-1) than the absorption rate constant (0.23 h-1) when administered orally as a non-retarded preparation. 6. The Renal Clearance of creatinine was slightly increased by pyridostigmine in volunteers and slightly decreased by pirenzepine in the total group of subjects.
Faiza Naseer - One of the best experts on this subject based on the ideXlab platform.
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Renal Clearance and Urinary Excretion of Roxithromycin in Healthy AdultFemale Subjects
European Journal of Experimental Biology, 2017Co-Authors: Shaneel Kousar, Hira Naeem, Zunaira Alina, Laiba Riaz, Syeda Fiza Raza Bukhari, Huma Naz, Ayesha Shahzad, Abida Niazi, Faiza NaseerAbstract:Objective: In current study, influence of environmental situation and genetic variations on Renal Clearance and urinary excretion of roxithromycin was determined in local healthy adult female subjects. Roxithromycin is a secondgeneration macrolide widely used in human clinics for different infectious diseases. Methods: For experimentation, ten healthy adult female were selected. Roxithromycin 300 mg (Rulide®) was given to each volunteer. Blank samples each for urine and blood was collected prior administration of roxithromycin and after that blood samples were collected at 1,2, 4 and 6 hours and urine samples were collected at 1, 2, 4, 6, 8, 10, 12, 24 and 48 hours post medication. Blood samples were centrifuged to separate plasma. A high performance liquid chromatography (HPLC) method was used to find out the concentration of drug in urine and plasma samples. In plasma and urine concentration of drug and endogenous creatinine were used to calculate Renal Clearance and urinary excretion of drug. Results: In present study the Renal Clearance of roxithromycin was 0.08 ± 0.01 ml/min/kg. Mean ± SE value for Clearance ratio between drug Clearance and creatinine Clearance was 0.04 ± 0.00 which indicates reabsorption (back diffusion) of roxithromycin. The cumulative percentage of oral dose of 300 mg tablet of roxithromycin excreted through urine during 48 hours was 12.87 ± 1.31 percent. Conclusion: Renal Clearance and urinary excretion observed in present study variates from previous studies conducted in other geographical regions under different environmental conditions. Variations in present study may be due to genetic variations. It is concluded from the study that Renal Clearance and urinary excretion study is required under indigenous conditions.
B. Eiermann - One of the best experts on this subject based on the ideXlab platform.
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Renal Clearance of pyridostigmine in myasthenic patients and volunteers under the influence of ranitidine and pirenzepine
Xenobiotica, 1993Co-Authors: B. Eiermann, N. Sommer, D. Winne, U. Maier, Fritz Schumm, Ursula Breyer-pfaffAbstract:1. To assess the contribution of tubular secretion to the Renal excretion of pyridostigmine, and its modification by other cationic drugs, six volunteers were given single oral doses of 60-mg pyridostigmine bromide with and without co-administration of ranitidine or pirenzepine. Renal Clearances were determined by h.p.l.c. analysis of pyridostigmine and enzymic measurement of endogenous creatinine in plasma and urine.2. In patients with myasthenia receiving continuous pyridostigmine therapy, Renal Clearance values were obtained in the same manner with and without ranitidine (10 patients) or pirenzepine (nine patients) co-medication.3. Pyridostigmine was not bound to plasma proteins. Its Renal Clearance averaged 6.65 ml/min per kg (350% of the creatinine Clearance) in all subjects, 74% being due to net tubular secretion.4. Mean values for pyridostigmine Renal Clearance and for Clearance by secretion were decreased in the presence of pirenzepine, but plasma concentrations were not affected significantly. Ra...
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Renal Clearance of pyridostigmine in myasthenic patients and volunteers under the influence of ranitidine and pirenzepine
Xenobiotica; the fate of foreign compounds in biological systems, 1993Co-Authors: B. Eiermann, N. Sommer, D. Winne, U. Maier, Fritz Schumm, Ursula Breyer-pfaffAbstract:1. To assess the contribution of tubular secretion to the Renal excretion of pyridostigmine, and its modification by other cationic drugs, six volunteers were given single oral doses of 60-mg pyridostigmine bromide with and without co-administration of ranitidine or pirenzepine. Renal Clearances were determined by h.p.l.c. analysis of pyridostigmine and enzymic measurement of endogenous creatinine in plasma and urine. 2. In patients with myasthenia receiving continuous pyridostigmine therapy, Renal Clearance values were obtained in the same manner with and without ranitidine (10 patients) or pirenzepine (nine patients) co-medication. 3. Pyridostigmine was not bound to plasma proteins. Its Renal Clearance averaged 6.65 ml/min per kg (350% of the creatinine Clearance) in all subjects, 74% being due to net tubular secretion. 4. Mean values for pyridostigmine Renal Clearance and for Clearance by secretion were decreased in the presence of pirenzepine, but plasma concentrations were not affected significantly. Ranitidine caused a small non-significant decrease of the pyridostigmine Clearance in patients. 5. Pyridostigmine had a higher elimination (2 h-1) than the absorption rate constant (0.23 h-1) when administered orally as a non-retarded preparation. 6. The Renal Clearance of creatinine was slightly increased by pyridostigmine in volunteers and slightly decreased by pirenzepine in the total group of subjects.
Pertti J. Neuvonen - One of the best experts on this subject based on the ideXlab platform.
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gemfibrozil increases plasma pravastatin concentrations and reduces pravastatin Renal Clearance
Clinical Pharmacology & Therapeutics, 2003Co-Authors: Carl Kyrklund, Jt T Backman, Mikko Neuvonen, Pertti J. NeuvonenAbstract:Background: Gemfibrozil increases the plasma concentrations of active acid forms of cerivastatin, lovastatin, and simvastatin. Pravastatin pharmacokinetics differs from those of these 3 statins, which are extensively metabolized. Our aim was to study the effects of gemfibrozil on the pharmacokinetics of pravastatin. Methods: A randomized, placebo-controlled, 2-phase crossover study was carried out. Ten healthy volunteers took gemfibrozil (1200 mg/d) or placebo for 3 days. On day 3, each subject ingested a single 40-mg dose of pravastatin. The concentrations of pravastatin and gemfibrozil in plasma and the cumulative excretion of pravastatin into urine were measured up to 24 hours. Results: During the gemfibrozil phase, the mean total area under the plasma concentration–time curve (AUC) of pravastatin from 0 hours to infinity was 202% (range, 40%-412%) of the corresponding value during the placebo phase (P < .05), but there was no difference in the half-life between the phases. The Renal Clearance of pravastatin was reduced from 25 L/h to 14 L/h by gemfibrozil (P < .0001), but the cumulative excretion of pravastatin into urine did not change significantly. The increase in the AUC of pravastatin from 0 to 24 hours correlated significantly with the decrease in the Renal Clearance of pravastatin (r = 0.72, P = .02). However, the change in Renal Clearance was only a minor contributor to the increase in pravastatin AUC. Conclusions: Gemfibrozil increases plasma concentrations of pravastatin. This is partly but not solely the result of the reduced Renal Clearance of pravastatin. The increase in pravastatin AUC from 0 hours to infinity by gemfibrozil may represent an interference with a transport protein. Clinical Pharmacology & Therapeutics (2003) 73, 538–544; doi: 10.1016/S0009-9236(03)00052-3
