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 volunteers were also given a single oral dose of 300 mg mofarotene. The data indicate a similar disposition for mofarotene in all species studied: low clearance consistent with a high bioavailability following oral dosing, and large volume of distribution indicating an extensive tissue uptake. Also in vitro in liver microsomes, the values for intrinsic clearance were in all species within a 2-fold range. The dog, however, tended to exhibit, both in vitro and in vivo, the lowest clearance. Although (due to the lack of protein binding data) a direct prediction 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 studied including man.