Disposition and Metabolism of Minaprine in the Rat

Abstract

1. After iv. injection (5 mg/kg) to rats, minaprine is cleared rapidly from plasma with an elimination t_1/2 of 34 min. After the same dose, but given orally the drug is rapidly absorbed from the rat gastrointestinal tract. The ratio of the area under the curves (AUC) of the parent drug indicates low bioavailability (5%).

2. Two metabolites of minaprine (M₃ and M₅) appeared rapidly in rat plasma and far exceed minaprine concentrations. Other known urinary metabolites of the drug were undetectable in rat plasma and brain within the limits of the sensitivity of the method.

3. Minaprine rapidly enters the central nervous system and then distributes almost evenly in various regions beyond the blood/brain barrier. It concentrates in brain tissue reaching concentrations two-three times those in plasma. Its metabolites enter the brain less rapidly and their brain AUC never reached 50% of the plasma AUC.