IN-VIVO AND IN-VITRO KINETICS OF MOFAROTENE IN MOUSE, RAT, DOG AND MAN

The pharmacokinetics of mofarotene were investigated in mice, rats and dogs following single intravenous and oral administrations. Healthy v olunteers were also given a single oral dose of 300 mg mofarotene. The data indicate a similar disposition for mofarotene in all species stu died: low clearance consistent with a high bioavailability following o ral dosing, and large volume of distribution indicating an extensive t issue uptake. Also in vitro in liver microsomes, the values for intrin sic clearance were in all species within a 2-fold range. The dog, howe ver, tended to exhibit, both in vitro and in vivo, the lowest clearanc e. Although (due to the lack of protein binding data) a direct predict ion of the in vivo clearance from in vitro data was not possible, the experiments with liver microsomes did provide a clear insight into the rate of elimination of mofarotene in vivo in the different species st udied including man.