Absorption, distribution and excretion of [14C] zonisamide after consecutive administration in rats

Absorption, distribution and excretion of [14C] zonisamide were studied in rats after 14 consecutive daily oral administration at the dose of 20 mg/kg. 1. Plasma levels at 24 hr after each administration tended to elevate slightly on 10 th day and became 1.2 fold of those after single administration. Maximum levels after the last administration, of about 17.4μg eq./ml were reached at 3 hr and decreased with half life of about 7.0 hr, and were virtually similar to that after single administration. 2. After repeated administration, the levels in plasma and most tissues were 1.2-1.5 times as high as those after single administration. At the time of the maximal plasma levels, most tissue levels were within the range of 2 fold of plasma levels except for levels in preputial gland, erythrocytes and liver. The distribution was similar to that after single administration. Autoradiographic findings on the distribution were essentially consistent with radiometric results. 3. During repeated administration, urinary excretion of radioactivity were virtually constant at about 80% of dose after second administration, and fecal excretion, about 10% after 7th administration. Within 120 hr after the last administration, urinary and fecal excretion amounted to about 83% and 13%, respectively. The excretion was similar to that after single administration.