TOXICOKINETICS OF [H-3] SAXITOXINOL IN PERIPHERAL AND CENTRAL-NERVOUS-SYSTEM OF RATS

This study evaluated the toxicokinetics of a saxitoxin (STX) analog, [ H-3]saxitoxinol (STXOL), in rats. [H-3]saxitoxinol (18.9 mu Ci/kg body weight) was administered iv to male Wistar rats via the penile vein, After injection, [H-3]STXOL disappeared rapidly from plasma (t 1/2 = 2 9.3 min), and 75% of the radiolabel was cleared from plasma within 2 h r. Radioactivity associated with red blood cell membranes was inversel y related with the radioactivity associated with hemoglobin, suggestin g internalization of STXOL, Distribution of [H-3]STXOL, 48 hr after iv exposure, showed that muscle tissues retained 91.2 +/- 7.1%, liver 63 .7 +/- 3.8%, heart 17.4 +/- 1.6%, and lung 9.2 +/- 0.8% of the residua l dose, High-performance liquid chromatography (HPLC) analysis for sax itoxinol showed three to four major radiolabeled peaks for each of the se tissues, By 48 hr, radiolabel associated with the saxitoxinol peak decreased 95% in lungs, heart, and kidneys, with a concomitant increas e in unidentified, more polar peaks, No STXOL metabolites were detecte d in the urine from these animals, Radioactivity accumulation in the b rain increased to a maximum of 162% at 8-hr postexposure, compared to values obtained at 10 min, then gradually declined to 148% by 48 hr, H PLC analysis of brain extracts showed that the relative percentage of radioactivity associated with parent toxin gradually decreased, with a concomitant rise in the levels of more polar peaks, Similar results w ere obtained for spinal cord, The data suggest that saxitoxinol was ra pidly cleared from most of the peripheral organs and was little, if an y metabolized by muscle cells. (C) 1996 Academic Press, Inc.