ROLE OF ACIDIC PHOSPHOLIPIDS IN TISSUE DISTRIBUTION OF QUINIDINE IN RATS

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The mechanism of interorgan variation in tissue distribution of quinidine was investigated from a viewpoint of binding characteristics to phospholipids and the composition of phospholipids in various tissues. The order of binding of quinidine to an individual standard phospholipid, expressed as a product of the association constant (K) and the number of binding sites (n), was : phosphatidyl ethanolamine (PhE)<dipalmitoyl phosphatidyl choline (saturated PhC)≧phosphatidyl choline (unsaturated PhC)<phosphatidyl inositol (PhI)<phosphatidyl glycerol (PhG)<phosphatidic acid (PhA)<phosphatidyl serine (PhS). Thus, quinidine was found to bind preferentially to acid phospholipids such as PhS, PhA, PhG, and PhI. The greatest binding was obtained in PhS among the various phospholipids and was more than 300-fold that of neutral phospholipids such as PhC and PhE. The concentration of individual components of phospholipids in the lung, kidney, liver and heart was determined using a two dimensional thin-layer chromatography. The concentration of PhS, highly responsible for the quinidine binding to phospholipids in each tissue, was ranked in the following order : heart<liver<kidney<lung. The contribution of PhS to quinidine binding was more than 86% in all tissues. A good correlation between the concentration of PhS in each tissue and the C_t/C_p ratio in vivo was obtained (r=0.984). Thus, it was concluded that the tissue distribution of quinidine in vivo depended on the composition of phospholipids in tissues and that a determinant of interorgan variation in the tissue distribution of quinidine was the concentration of PhS in the tissues.

ROLE OF ACIDIC PHOSPHOLIPIDS IN TISSUE DISTRIBUTION OF QUINIDINE IN RATS

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