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EC number: 201-064-4 | CAS number: 77-86-1
The volume of the central compartment (223 mL/kg) was similar to the volume of the inulin space (data not given). Therefore the authors concluded that TRIS initially distributes to the extracellular space. The final volume of distribution of TRIS (3641 mL/kg) however, is much larger than the inulin space (275 mL/kg), which can only be explained by an accumulation of the drug inside cells.
Intracellular accumulation would be expected from the physicochemical properties of TRIS. Since the drug is a weak base with a pK-value of 7.92, 70% of the administered amount exists in the cationic form at normal plasma pH. Assuming that only the undissociated from can pass the cell membrance, the normal transmembrane pH-gradient may create a 2 -3 -fold higher intracellular drug concentration due to pH-partitioning. The observed drug levels in erythrocytes and the drug concentrations calculated for the peripheral compartments fit into this concept. In situations of elevated extracellular pH the accumulation of TRIS inside cells should be even greater. But the buffer capacity of plasma probably prevented a long-lasting rise of extracellular pH after infusion of TRIS solution of pH 10.9 and thus the results obtained with both solutions were identical.
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