Abstract:

The purpose of this study is to characterize the tissue distribution, excretion and pharmacokinetics profiles of R-hap in healthy Wistar rats. R-hap was radiolabeled by the IODO-GEN method. Tissue distribution and urinary, fecal and biliary excretion patterns of 125I-R-hap were investigated following a single i.v. bolus injection. Pharmacokinetics properties of 125I-R-hap were also examined after a single i.v. bolus injection. The trichloroacetic acid (TCA) precipitated radioactivity was widely distributed and rapidly diminished in most tissues. Kidney contained the highest radioactivity among all organs and the distribution of 125I-R-hap to fat was minimal. The cumulative excretion of 125I-R-hap reached 71.81% ± 2.15% of the administered radioactivity at 48 h and 94.71% ± 1.50% at 120 h. Urinary excretion was the dominant route of elimination following i.v. administration, as 80.64% ± 1.47% and 14.07% ± 0.95% of administered radioactivity were recovered in urine and feces, sectively, in intact rats over 120 h. The mean areas under the plasma concentration-time curve was (8818.4 ± 576.1) Bq/h/mL. The results of tissue distribution, excretion and pharmacokinetics of R-hap in rats provided biopharmaceutical basis for the design of future clinical trials.

Key words: R-hap, R-hap, Tissue distribution, Tissue distribution, Excretion, Excretion, Pharmacokinetics, Pharmacokinetics