TISSUE DISTRIBUTION OF (8-C-14)-OCTACOSANOL IN LIVER AND MUSCLE OF RATS AFTER SERIAL ADMINISTRATION

The present study investigates the metabolic disposition of octacosanol in liver and muscle of rats after serial doses administration. Three groups of experimental animals received various doses of (8-C-14)-octacosanol (2.0 mu Ci/dose) orally through a stomach tube. When expressed per organ, the highest amount of radioactivity was found in the liver (9.5% of administered dose), followed by the digestive tracts (8.2%) and the muscle (3.5%) at all doses of administration. The radioactivity in all other tissues examined was insignificant (<0.9% in each) at any time during this period. The radioactivity in liver disappeared rapidly after 2-dose administration, even when the doses were increased. In contrast, the muscle seemed to be able to store a considerable amount of octacosanol in response to doses of administration. In case of 9-dose serial administration, after 3 and 9 days the accumulation of radioactivity in muscle was higher than that of the liver, possibly due to slow elimination of radioactivity from muscle. By the time when radioactivity in liver and muscle was low (after 6 and 10 doses), the radioactivity of octacosanol in plasma reached a maximum, particularly after administration of 6 doses. The plasma concentration and the fecal excretion of the radioactivity of octacosanol reached a maximum at the third day after the oral 6 doses, which reflected not only the saturation of radioactivity uptake by liver and muscle but also the metabolism and excretion of octacosanol with time at the same period. The results are discussed in the light of the role of octacosanol in increasing muscle endurance in exercise.