Alteration of the pharmacokinetics of aminoglycosides by adsorption in a filter during continuous renal replacement therapy. An in vitro assessment

Objectives. - Filters used in continuous renal replacement therapy (CRRT) induce elimination by filtration, dialysis, and adsorption. The worldwide used ST150 (R) filter adsorbs cytokines. However, adsorption is a non-specific process which might alter the pharmacokinetics of drugs. Pharmacodynamic/pharmacokinetic relationship of aminoglycosides evidences the importance of the peak concentration at the first dose. We hypothesize an in vitro study may clarify the routes of elimination of aminoglycosides using the ST150 (R) filter. Methods. - Prismaflex (R) and the STX150 (R) filter, Baxter-Gambro were used. The diafiltration mode combined flowrates of dialysis and filtration at 2.5/1.5 L/h, respectively, over 6 h. One ionic solute was used in the different compartments. Pharmacokinetic analyses were performed using the NeckEpur(R) software. Results. - Percentages of gentamicin, tobramycin, and amikacin eliminated from the central compartment were 97 +/- 1, 95 +/- 3, and 94 +/- 6, %, respectively. The clearances were 8.4 +/- 2.3, 5.4 +/- 5, and 4.2 +/- 0.4 L/h, respectively. The contributions of dialysis, filtration, and adsorption for gentamicin, tobramycin, and amikacin were 34.3 +/- 2.1, 0 +/- 0, and 67.7 +/- 2.1; 51.1 +/- 1.6, 6.3 +/- 3.1, and 46.3 +/- 2.0, and 37.8 +/- 6.3, 46.3 +/- 2.0, and 16.0 +/- 5.7%, respectively. Among physico-chemical properties, the rate of adsorption linearly and inversely correlated with the polar surface area of aminoglycosides (Y = -0.44 X + 161.7; R-2 = 0.9993). Discussion. - Using the ST150 (R) filter, dialysis, filtration, and adsorption play a role depending on the chemical structure of aminoglycosides. In the diafiltration mode, elimination of gentamicin and tobramycin by filtration is not detected or weak, respectively. Adsorption should be considered as a potential adverse effect of CRRT. Polar surface area of drugs is a physico-chemical parameter which should be considered regarding adsorption of drugs in filters. The risk needs to be systematically assessed. (C) 2020 Societe francaise de pharmacologie et de therapeutique. Published by Elsevier Masson SAS. All rights reserved.