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Adsorption of nafamostat mesilate by hemodialysis membranes
O Inagaki1, Y Nishian, R Iwaki
1Department of Kidney and Dialysis, Hyogo College of Medicine, Nishinomiya, Japan.
Abstract:
The adsorption of the anticoagulant nafamostat mesilate (FUT-175) by five different hemodialysis membranes was studied in vivo and in vitro. In vivo, FUT-175 was adsorbed strongly by a polyacrylonitrile (AN69) membrane and slightly by another polyacrylonitrile (J-PAN) membrane but not by Cuprophan (CU), hemophan (HE), or polymethylmethacrylate (PMMA) membranes during hemodialysis performed in 4 patients in whom FUT-175 was used as an anticoagulant. Only during hemodialysis using the AN69 membrane did FUT-175 not induce a significant prolongation of celite-activated coagulation time. In vitro studies showed that FUT-175 was adsorbed by the AN69, J-PAN, and PMMA membranes but not by the CU and HE membranes. Methylene blue, a dye that possesses a cationic portion in its chemical structure, stained AN69, J-PAN, and PMMA membranes. Since FUT-175 also possesses a cationic portion, we conclude that FUT-175 is adsorbed by negatively charged membranes via an ionic bond and is unsuited for use as an anticoagulant in hemodialysis using an AN69 membrane because of that membrane's marked capacity to adsorb FUT-175.
Insights
Nafamostat mesilate (FUT-175) strongly adsorbs to polyacrylonitrile (AN69) hemodialysis membranes, reducing its anticoagulant effectiveness. This adsorption, driven by ionic bonds, makes FUT-175 unsuitable for AN69 membranes.
Area of Science:
- Biomaterials Science
- Nephrology
- Pharmacology
Background:
- Nafamostat mesilate (FUT-175) is an anticoagulant used during hemodialysis.
- Hemodialysis membranes can interact with and adsorb drugs, potentially affecting their efficacy.
- Understanding drug-membrane interactions is crucial for optimizing anticoagulation therapy.
Purpose of the Study:
- To investigate the adsorption of nafamostat mesilate (FUT-175) by various hemodialysis membranes.
- To determine the impact of FUT-175 adsorption on its anticoagulant activity in vivo and in vitro.
- To elucidate the mechanism of FUT-175 adsorption by hemodialysis membranes.
Main Methods:
- In vivo and in vitro adsorption studies of FUT-175 with five hemodialysis membranes (AN69, J-PAN, Cuprophan, Hemophan, PMMA).
- Measurement of celite-activated coagulation time in patients undergoing hemodialysis with FUT-175.
- Staining of membranes with methylene blue to assess charge characteristics.
Main Results:
- FUT-175 was strongly adsorbed by the polyacrylonitrile (AN69) membrane and slightly by the J-PAN membrane in vivo and in vitro.
- No significant adsorption of FUT-175 was observed with Cuprophan (CU), Hemophan (HE), or polymethylmethacrylate (PMMA) membranes.
- FUT-175 did not prolong celite-activated coagulation time during hemodialysis with the AN69 membrane.
- Methylene blue staining indicated that AN69, J-PAN, and PMMA membranes possess negative charges.
Conclusions:
- Nafamostat mesilate (FUT-175) adsorbs to negatively charged hemodialysis membranes, such as AN69, J-PAN, and PMMA, via ionic bonding.
- The strong adsorption of FUT-175 by the AN69 membrane compromises its anticoagulant function.
- FUT-175 is unsuitable for use as an anticoagulant with AN69 hemodialysis membranes due to significant drug adsorption.
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