Absorption, distribution and excretion of zenarestat, a new aldose reductase inhibitor, in rats and dogs

Abstract

1. The absorption, distribution and excretion of zenarestat have been studied in male rats and dogs after i.v. and oral administration of ¹⁴C-zenarestat.

2. The bioavailability of zenarestat was 93% in rats and 65% in dogs. A major proportion of the plasma ¹⁴C in rats and dogs was due to unchanged drug. The terminal elimination half-life of zenarestat in plasma was 6 h in rats and dogs.

3. Except for organs associated with absorption and elimination, tissue ¹⁴C levels were lower than plasma levels in rats. The distribution to, and elimination from sciatic nerve were slower than those of other tissues.

4. Most of the ¹⁴C from ¹⁴C-zenarestat administered orally and i.v. to rats and dogs was excreted in the faeces. After i.v. dosing to bile duct-cannulated rats, 96% of the radioactive dose was excreted in the bile.