Pharmacokinetics of epinastine and a possible mechanism for double peaks in oral plasma concentration profiles

The pharmacokinetics of epinastine (EPN), an anti-allergic agent, was inves tigated in rats. The plasma concentration-time profile of EPN after intrave nous (i.v.) administration was triexponential. After oral administration of EPN (7.5 and 20 mg/kg), the drug was rapidly absorbed, and C-max was reach ed 2 h after dosing. A minor secondary peak was observed in EPN plasma conc entration-time profiles at both doses. The bioavailability of EPN after ora l dosing was 41 and 40%, The kinetic parameters (T-1/2, AUC and MRT) for un labeled EPN were much smaller than those for C-14-EPN, which has already be en reported. The total biliary excretion of EPN at a 7.5 mg/kg dose was 15. 5% of the dose, but the percentage of conjugates in bile was extremely low and about 11% of the total biliary excretion. The increase in the plasma co ncentration in bile duct-linked rats after oral administration of EPN (20 m g/kg) was not observed, indicating that a secondary increase in drug concen tration based on enterohepatic circulation was ruled out. When the gastroin testinal (GI)-transit of phenol red (PR) after oral administration of EPN ( 20 mg/kg) was estimated, the GI-transit of PR was significantly delayed, an d at 3-4 h after dosing half of the PR dose reached the jejunum, The remain ing EPN in the small intestine after oral administration (7.5 mg/kg) reache d peak levels 2 h after dosing, but then partly increased again at 4 h, As a result, it was clarified that the double peaks observed after oral doses are mainly due to the delayed absorption of a part of EPN. based on the red uction in gastric motility caused by the drug.