Inhibitory effect of free fatty acids on plasma protein binding of disopyramide in haemodialysis patients |
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Authors: | T Horiuchi I Johno T Hasegawa S Kitazawa M Goto T Hata |
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Institution: | (1) Department of Hospital Pharmacy, School of Medicine, Nagoya University, Nagoya, Japan;(2) Department of Hospital Pharmacy, Nagoya Memorial Hospital, Nagoya, Japan;(3) Department of Internal Medicine, Shinseikai Dai-ichi Hospital, Nagoya, Japan;(4) Present address: Pharmacy Services, Kishiwada City Hospital, Kishiwada, Japan |
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Abstract: | Summary The plasma (or serum) protein binding of disopyramide (DSP) in five haemodialysis patients was studied using an ultrafiltration
technique. There was an increase in the free fraction of DSP in the plasma on dialysis days in comparison to the levels on
interdialysis days, which was associated with an elevation of the free fatty acid levels in the plasma together with the increase
of the free fraction of DSP. The inhibitory effect of free fatty acids on DSP binding in an in vitro study was enhanced in
proportion to their concentrations, and was shown to be due to competition at one binding site by experiments with oleic acid
as a representative displacer.
Certain endogenous organic acids, such as indoxyl sulphate, 2-hydroxyhippuric acid and hippuric acid, which are characteristically
elevated in chronic renal failure, scarcely affected the protein binding of DSP. The findings indicate that free DSP should
be monitored in patients with elevated plasma free fatty acid levels, such as those on haemodialysis therapy. |
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Keywords: | disopyramide haemodialysis protein binding intraindividual variability free fatty acids competitive inhibition |
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