Metabolic Fate of Lactitol (NS-4). (II). Distribution, Transfer to Fetus and Milk after Single Administration and Metabolic Fate, Effect on the Hepatic Drug-Metabolizing Enzyme Activities after Repeated Administration in Rats.

Abstract

Distribution, transfer to fetus and milk were studied after single oral administration of 14C-lactitol to rats. Further, the absorption, metabolism, distribution, excretion and the effect on hepatic drug-metabolizing enzyme activities were also studied after repeated oral administration of 14C-lactitol or unlabeled lactitol to rats. 1. After single oral administration to male rats, the radioactivity was extensively distributed to the tissues except the central nervous system, eyeball, fat, skeletal muscle, aorta and testis. The radioactivity levels in the tissues reached the maximum level 10 hr after dosing and decreased slowly. There were no clear differences in the tissue distribution of radioactivity between male and female rats. 2. In pregnant rats, the radioactivity was higher in the fetus than in the maternal blood. 3. In lactating rats, the radioactivity was higher in the milk than in the plasma. 4. During 21-day consecutive oral administrations, the radioactivity in tissues accumulated gradually. After the 21st dose the radioactivity was eliminated from tissues more slowly than after the 1st dose. 5. The residual radioactivity present in tissues after single or repeated oral administration was considered to be that incorporated into tissue components, such as proteins and lipids. 6. The repeated oral administration of lactitol had no effect on the hepatic drug-metabolizing enzyme activities.