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

Abstract

The 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 vitro CHDF experiments with a polyacrylonitrile (PAN) membrane were first performed using these antibiotics, and then the clearances were compared with in vivo CHDF situations determined in 16 critically ill patients. The in vitro CHDF clearances were described as the product of the outflow rate of a drain (Q outflow ) 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 observed in vivo clearances also agreed very well with the predicted values, with a product of Q outflow and plasma unbound fraction, when residual creatinine clearance (CL CR ) 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 that Q outflow and residual CL CR are major determinants of the dosage and dosing interval for these antibiotics. Although the applicability needs to be confirmed with another type of membrane or higher Q outflow , our nomogram can help determine the dosage setting in critically ill patients receiving CHDF.

Tedizolid Adsorption and Transmembrane Clearance during in vitro Continuous Renal Replacement Therapy

“…Some found substantial drug adsorption, necessitating dosage adjustment [7,10] . Others reported no significant effect of drug adsorption [22] . Drug adsorption seemed to be drug-and membrane-specific.…”

“…The current CRRT drug dosing practice assumes that the effect of drug adsorption to extracorporeal drug clearance is minimal. Assessment of adsorption onto the hemodiafilter membrane and extracorporeal circuit has been conducted for only a few antibiotics [7,10,22,23] . Some found substantial drug adsorption, necessitating dosage adjustment [7,10] .…”

High variability of teicoplanin concentration in patients with continuous venovenous hemodiafiltration

“…However, pharmacokinetic studies for maintenance dosages of teicoplanin are limited. Current recommendations for patients receiving CRRT originate from either pharmacokinetic estimates of studies with a few patients and different doses of CRRT than are used today . Insufficient current pharmacokinetic data limit evidence‐based dose recommendations for patients .…”

“…Current recommendations for patients receiving CRRT originate from either pharmacokinetic estimates of studies with a few patients and different doses of CRRT than are used today. 14,15 Insufficient current pharmacokinetic data limit evidence-based dose recommendations for patients. 3 Therefore, the objective of this prospective observational study was to evaluate the pharmacokinetics of teicoplanin as maintenance therapy in patients receiving CVVHDF with contemporary equipment and prescriptions.…”

Pharmacokinetic Assessment in Patients Receiving Continuous RRT

“…While standard noncompartmental modeling may be used to calculate key pharmacokinetic parameters, the time course for drug concentrations in the plasma, effluent, and urine (when available) can also be subjected to compartmental modeling using a population-based approach (36)(37)(38). Based on the model that best describes the data, covariate relationships can be evaluated to describe the effect of covariates such as treatment and patient variables (e.g., Q E , body weight) on the pharmacokinetic model parameters (such as clearance and V D ).…”