[Kinetics of THAM (TRIS) distribution in intra- and extracellular compartments]

The distribution of 14C labelled THAM (tris-hydroxymethylaminomethane) was determined between intra- and extracellular space of nephrectomised Sprague-Dawley rats as a function of time at constant plasma pH of 7.4. The following results were obtained: An equilibrium in the distribution of THAM between ECS and ICS will not occur before 6-12 hours after administration. This indicates that THAM permeates very slowly into the intracellular compartment, which is in contrast to the general assumption that it quickly diffuses into the intracellular space to restore the intracellular acidosis. THAM disappears from the extracellular space in a multiexponential fashion, indicating that it equilibrates with the different body tissues at largely variable rates. The equilibrium which occurs between both body compartments 6-12 hours after THAM application does not agree with the values which are expected for transfer of only the nonionised substance. At plasma pH 7.4 and a "mean whole body pHi" of 6.88, THAM is distributed with a distribution ratio of 4 (ICS/ECS), a value quite different from the value of 11 which would be expected for exclusive nonionic diffusion. Thus THAM is also transferred across the cell membrane in ionised form. These results indicate that the influx of THAM into the intracellular space is too slow (when compared to the renal elimination kinetics) to influence intracellular pH significantly by direct buffer action. Moreover, only a fraction of THAM enters the intracellular space in the nonionised form, thus reducing (to an even greater extent) the direct effect of THAM on the intracellular acid-base equilibrium.