Influence of arterio‐venous haemofiltration on teicoplanin elimination.

Hillaire‐Buys, Dominique; Peyrière, Hélène; Lobjoie, E; Brès, J.; Ossart, M; Despaux, E

doi:10.1111/j.1365-2125.1995.tb04543.x

Cited by 10 publications

(3 citation statements)

References 5 publications

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“…Hence, wrong conclusion would be drawn from the calculations based on the conventional approaches not accounting for adsorption. The fraction of teicoplanin removed via dialysis was very small, which was in line with the previous studies [27].…”

Section: Teicoplaninsupporting

confidence: 92%

An Integrated Dialysis Pharmacometric (IDP) Model to Evaluate the Pharmacokinetics in Patients Undergoing Renal Replacement Therapy

et al. 2020

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Purpose Clearance via renal replacement therapy (RRT) can significantly alter the pharmacokinetic profile of drugs. The aim of this study was (i) to improve the use of clinical trial data and (ii) to provide a model that allows quantification of all aspects of drug elimination via RRT including adsorption to dialysis membranes and/or degradation of the drug in the dialysate. Methods An integrated dialysis pharmacometric (IDP) model was developed to simultaneously incorporate all available RRT information. The sensitivity, accuracy and precision of the IDP model was compared to conventional approaches in clinical trial simulations and applied to clinical datasets of teicoplanin and doripenem. Results The IDP model was more accurate, precise and sensitive than conventional plasma-concentration-based approaches when estimating the clearance RRT (relative bias <1%). In contrast to conventional approaches, adsorption and degradation were quantifiable using the IDP model (relative bias: −1.1% and − 1.9%, respectively). Applied to clinical data, clearance RRT , drug degradation (effluent-half-life doripenem : 13.5 h −1 ) and adsorption (polysulphone adsorption capacity teicoplanin : 31.2 mg) were assessed. Conclusion The IDP model allows accurate, precise and sensitive characterization of clearance RRT , adsorption and degradation. Successful quantification of all aspects of clearance RRT in clinical data demonstrated the benefit of the IDP model as compared to conventional approaches. KEY WORDS adsorption . doripenem . pharmacokinetics . renal replacement therapy . teicoplanin ABBREVIATIONS CVVHD Continuous veno-venous hemodialysis CVVH Continuous veno-venous hemofiltration CVVHDF continuous veno-venous hemodiafiltration dOFV Drop in objective function value Eq. Equation IDP model Integrated dialysis pharmacometric model LLP-SIR log-likelihood-profiling based samplingimportance-resampling rBias relative Bias Astrid Broeker and Matthias G. Vossen contributed equally to this work.

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Section: Teicoplaninsupporting

confidence: 92%

An Integrated Dialysis Pharmacometric (IDP) Model to Evaluate the Pharmacokinetics in Patients Undergoing Renal Replacement Therapy

et al. 2020

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“…The pharmacokinetics of teicoplanin has been studied and is known to vary under differing conditions, including renal impairment 12 , renal support therapies 13 , elderly 14 , and neutropenia 15 . MRSA infections may occur frequently on such immunocompromised hosts.…”

Section: Introductionmentioning

confidence: 99%

Variability in Teicoplanin Protein Binding and Its Prediction Using Serum Albumin Concentrations

Yano

Nakamura

Tsukamoto

et al. 2007

Therapeutic Drug Monitoring

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The impact of lower serum albumin levels on teicoplanin pharmacokinetics has not been previously determined. The authors assessed the relationship between total and free concentrations of teicoplanin in serum samples obtained from patients receiving teicoplanin therapy for Gram-positive bacterial infections. In addition, the authors determined the contribution of serum albumin concentrations to the unbound fraction of teicoplanin. One hundred ninety-eight serum samples were obtained from 65 patients undergoing routine therapeutic drug monitoring of teicoplanin. Free serum teicoplanin was separated by ultrafiltration, and total and free serum concentrations of teicoplanin were determined by a fluorescence polarization immunoassay. Regression analysis was then performed to build a prediction model for the free serum teicoplanin concentration from the total serum teicoplanin concentration and the serum albumin level using the first 132 samples. The predictive performance of this model was then tested using the next 66 samples. Free serum teicoplanin concentrations (Cf) (mug/mL) were predicted using a simple model constructed using total serum teicoplanin (Ct) (mug/mL) and albumin concentrations (ALB) (g/dL): Cf = Ct/(1 + 1.78 * ALB). This model could estimate free serum teicoplanin concentrations with a small bias and an acceptable error. The measured free level of teicoplanin will lie between 0.63 and 1.38 times the predicted concentration in 95% of cases. Serum albumin level plays a major role in the variability of the fraction unbound of teicoplanin. This model can reliably estimate free serum teicoplanin concentrations more easily than by using direct measurements.

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“…Similar major differences are described with ceftriaxone and teicoplanin in patients during renal replacement therapy [16][17][18]. Both antimicrobial drugs are highly protein bound as flucloxacillin and both drugs are not (ceftriaxone), or only to a small degree (teicoplanin), detected in the dialysate/ultrafiltrate.…”

Section: Pharmacokinetic Aspectsmentioning

confidence: 53%

How to Calculate Clearance of Highly Protein-Bound Drugs during Continuous Venovenous Hemofiltration Demonstrated with Flucloxacillin

Meyer

Gendy

Karth³

et al. 2003

Kidney Blood Press Res

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Background: Flucloxacillin is an important antimicrobial drug in the treatment of infections with Staphylococcus aureus and therefore is often used in staphylococcal infections. Furthermore, flucloxacillin has a high protein binding rate as for example ceftriaxone or teicoplanin – drugs which have formerly been characterized as not being dialyzable. Methods: The pharmacokinetic parameters of 4.0 g flucloxacillin every 8 h were examined in 10 intensive care patients during continuous venovenous hemofiltration (CVVH) using a polyamide capillary hemofilter. In addition, the difficulty of calculating the hemofiltration clearance of a highly protein-bound drug is described. Results: Flucloxacillin serum levels were significantly lowered (56.9 ± 24.0%) even though only 15% of the drug was detected in the ultrafiltrate. Elimination half-life, total body clearance and sieving coefficient were 4.9 ± 0.7 h, 117.2 ± 79.1 ml/min and 0.21 ± 0.09, respectively. These discrepancies can be explained by the high protein binding of flucloxacillin, the adsorbing property of polyamide and the equation in order to calculate hemofiltration clearance. The unbound fraction of a 4.0 g flucloxacillin dosage facilitates time above the minimum inhibitory concentration (T > MIC) of 60% only for strains up to a minimum inhibitory concentration (MIC) of 0.5 mg/l. Conclusion: Based on the data of this study, we conclude that intensive care patients with staphylococcal infections on CVVH should be treated with 4.0 g flucloxacillin every 8 h which was safe and well tolerated. Moreover, further studies with highly protein-bound drugs are recommended to check the classical ‘hemodialysis’ equation as the standard equation in calculating the CVVH clearance of highly protein-bound drugs.

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Influence of arterio‐venous haemofiltration on teicoplanin elimination.

Cited by 10 publications

References 5 publications

An Integrated Dialysis Pharmacometric (IDP) Model to Evaluate the Pharmacokinetics in Patients Undergoing Renal Replacement Therapy

An Integrated Dialysis Pharmacometric (IDP) Model to Evaluate the Pharmacokinetics in Patients Undergoing Renal Replacement Therapy

Variability in Teicoplanin Protein Binding and Its Prediction Using Serum Albumin Concentrations

How to Calculate Clearance of Highly Protein-Bound Drugs during Continuous Venovenous Hemofiltration Demonstrated with Flucloxacillin

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