1993 Volume 8 Issue 6 Pages 1241-1251
Absorption, distribution, and excretion of [14C] 4-amino-1-β-D-arabinofuranosyl-2(1H)-pyrimidinone 5'-(sodium octadecyl phosphate) monohydrate (YNK01) were studied during and after repeated administrations to rats once a day at 25mg/kg for the maximum of 21 days.
1. Blood concentration of [14C] YNK01 at 24 hours after dosing showed a tendency to increase with repetition.
2. Excretion of [14C] YNK01 in urine and feces at 24 hours after dosing did not show changes by increasing dosing times after the 7 th dosing, and no marked difference was observed compared with the single dose group.
3. After the 21st dosing, an in crease tendency in tissue concentration was observed in all tissues, except thymus and digestive tract. Tissue which showed the highest increase in concentration was the adipose tissue. Metabolite in the adipose tissue was assumed to be structure of more lipophilic properties that of YNK01.
4. The effect of YNK01 on the hepatic drug-metabolizing enzymes was examined after repeated administration of YNK01 for 10 days. A slight increase was observed in the P-450 content in the 75 mg/kg group. Significant, but dose-independent, increase in the activities of aminopyrine-N-demethylase and aniline hydroxylase was observed.
