MEASUREMENT OF THE EXTRAVASCULAR CONCENTRATION OF RENAL AGENTS FOLLOWING INTRAVENOUS BOLUS INJECTION

The extravascular concentration (Ce) of some renal agents, in relation to the simultaneous plasma concentration (Ci), was calculated as a function of time after intravenous injection. Four agents were studied: Cr-51-ethylenediamine tetraacetate (EDTA) (n = 11), I-125-hippuran (n = 11), Tc-99m- dimercaptosuccinic acid (DMSA) (n = 11) and Tc-99m-mercaptoacetyl triglycine MAG3 (n = 20). Plasma clearance curves were constructed from data acquired from multiple blood sampling and fitted with two exponentials. The extravascular content of tracer at any fine is equal to the injected dose remaining after subtraction of the intravascular tracer content and the total amount of tracer cleared from plasma. Mean Ce/Ci at equilibrium (defined as the time, > 120 min, when Ce/Ci reaches its maximum value) was 1.087 (S.D. 0.019) for EDTA, 1.73 (0.48) for hippuran, 0.37 (0.2) for DMSA and 0.64 (0.3) for MAG3. Corresponding clearance (F) values were 68 (13), 415 (149), 15.6 (9.5) and 214 (52) ml min-1 1.73 m-2. Ce/Ci correlated with F and was also related to protein binding in plasma. Extrapolation of the regressions of Ce/Ci on F to F = 0 at several time points after injection gives a curve of Ce/Ci (at F = 0) against time which represents the rate of equilibration of the tracer throughout its distribution volume that would be seen with zero clearance, and therefore allows measurement of the in vivo protein binding of the tracer in plasma. Protein binding was zero for EDTA, 30% for hippuran, 86% for DMSA and 88% for MAG3. Ce/Ci may be higher than expected from protein binding if the plasma clearance of the tracer is rapid, as for hippuran and MAG3, and may introduce error into plasma clearance curves based on gamma camera blood pool regions of interest.