scholarly journals Determining the mechanisms underlying augmented renal drug clearance in the critically ill: use of exogenous marker compounds

Critical Care ◽  
2014 ◽  
Vol 18 (6) ◽  
Author(s):  
Andrew A Udy ◽  
Paul Jarrett ◽  
Janine Stuart ◽  
Melissa Lassig-Smith ◽  
Therese Starr ◽  
...  
Keyword(s):  
Critically Ill ◽  
Drug Clearance ◽  
Marker Compounds ◽  
Renal Drug Clearance

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.

Renal Drug Clearance in Preterm Neonates: Relation to Prenatal Growth

2007 ◽  
Vol 29 (3) ◽  
pp. 284-291 ◽  
Author(s):  
Karel Allegaert ◽  
Brian J Anderson ◽  
John N van den Anker ◽  
Sophie Vanhaesebrouck ◽  
Francis de Zegher
Keyword(s):  
Drug Clearance ◽  
Preterm Neonates ◽  
Prenatal Growth ◽  
Renal Drug Clearance

scholarly journals Individualization of Piperacillin Dosing for Critically Ill Patients: Dosing Software To Optimize Antimicrobial Therapy

2014 ◽  
Vol 58 (7) ◽  
pp. 4094-4102 ◽  
Author(s):  
T. W. Felton ◽  
J. A. Roberts ◽  
T. P. Lodise ◽  
M. Van Guilder ◽  
E. Boselli ◽  
...  
Keyword(s):  
Linear Regression ◽  
Creatinine Clearance ◽  
Critically Ill ◽  
Critically Ill Patients ◽  
Drug Exposure ◽  
Volume Of Distribution ◽  
Drug Clearance ◽  
Dose Optimization ◽  
Optimization Software ◽  
The Impact

ABSTRACTPiperacillin-tazobactam is frequently used for empirical and targeted therapy of infections in critically ill patients. Considerable pharmacokinetic (PK) variability is observed in critically ill patients. By estimating an individual's PK, dosage optimization Bayesian estimation techniques can be used to calculate the appropriate piperacillin regimen to achieve desired drug exposure targets. The aim of this study was to establish a population PK model for piperacillin in critically ill patients and then analyze the performance of the model in the dose optimization software program BestDose. Linear, with estimated creatinine clearance and weight as covariates, Michaelis-Menten (MM) and parallel linear/MM structural models were fitted to the data from 146 critically ill patients with nosocomial infection. Piperacillin concentrations measured in the first dosing interval, from each of 8 additional individuals, combined with the population model were embedded into the dose optimization software. The impact of the number of observations was assessed. Precision was assessed by (i) the predicted piperacillin dosage and by (ii) linear regression of the observed-versus-predicted piperacillin concentrations from the second 24 h of treatment. We found that a linear clearance model with creatinine clearance and weight as covariates for drug clearance and volume of distribution, respectively, best described the observed data. When there were at least two observed piperacillin concentrations, the dose optimization software predicted a mean piperacillin dosage of 4.02 g in the 8 patients administered piperacillin doses of 4.00 g. Linear regression of the observed-versus-predicted piperacillin concentrations for 8 individuals after 24 h of piperacillin dosing demonstrated anr2of >0.89. In conclusion, for most critically ill patients, individualized piperacillin regimens delivering a target serum piperacillin concentration is achievable. Further validation of the dosage optimization software in a clinical trial is required.

scholarly journals The Pharmacokinetics of Oseltamivir and Oseltamivir Carboxylate in a Critically Ill Pediatric Patient Receiving Extracorporeal Membrane Oxygenation and Continuous Venovenous Hemodialysis

2012 ◽  
Vol 17 (2) ◽  
pp. 173-176 ◽  
Author(s):  
Rachel F. Eyler ◽  
Kristin C. Klein ◽  
Bruce A. Mueller
Keyword(s):  
Extracorporeal Membrane Oxygenation ◽  
Critically Ill ◽  
Standard Dose ◽  
Plasma Concentrations ◽  
Pediatric Intensive Care ◽  
Drug Clearance ◽  
High Dose ◽  
Oseltamivir Carboxylate ◽  
Membrane Oxygenation ◽  
Continuous Venovenous Hemodialysis

This report details the pharmacokinetics of oseltamivir and oseltamivir carboxylate following administration of high-dose oseltamivir in a critically ill child receiving extracorporeal membrane oxygenation (ECMO) and continuous venovenous hemodialysis (CVVHD). A 6-year-old critically ill male patient suffering from a presumed viral illness was transferred to our institution's pediatric intensive care unit from an outside hospital after developing respiratory failure and cardiomegaly. ECMO and oseltamivir therapy were initiated upon admission, and CVVHD was started on hospital day 3. Pharmacokinetic sampling occurred at an oseltamivir dose of approximately 4 mg/kg on hospital day 6. The patient's oseltamivir and oseltamivir carboxylate area under the plasma concentration time curves for the 12-hour dosing interval (AUC0–12) were 30.5 and 905 ng/mLhr, respectively. Drug clearance by CVVHD was 31.6 mL/min for oseltamivir and 26.9 mL/min for oseltamivir carboxylate. Pre- and postoxygenator oseltamivir and oseltamivir carboxylate plasma concentrations did not differ substantially. The patient's oseltamivir carboxylate plasma concentrations remained well above the reported mean 50% inhibitory concentration for 2009 pandemic H1N1 virus. However, despite receiving twice the standard dose of oseltamivir, the oseltamivir carboxylate AUC0–12 in our patient was less than that reported in noncritically ill pediatric subjects. The reduced oseltamivir carboxylate AUC0–12 found in our patient was most likely due to decreased drug absorption.

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