Pharmacokinetics of Epinastine and a Possible Mechanism for Double Peaks in Oral Plasma Concentration Profiles

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The pharmacokinetics of epinastine(EPN), an anti-allergic agent, was investigated in rats. The plasma concentration-time profile of EPN after intravenous(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 reached 2h after dosing. A minor secondary peak was observed in EPN plasma concentration-time profiles at both doses. The bioavailability of EPN after oral dosing was 41 and 40%. The kinetic parameters(T_<1/2> AUC and MRT)for unlabeled EPN were much smaller than those for ^<14>C-EPN, which has already been reported. The total biliary excretion of EPN at a 7.5mg/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 concentration in bile duct-linked rats after oral administration of EPN(20 mg/kg)was not observed, indicating that a secondary increase in drug concentration based on enterohepatic circulation was ruled out. When the gastrointestinal(GI)-transit of phenol red(PR)after oral administration of EPN(20 mg/kg)was estimated, the GI-transit of PR was significantly delayed, and at 3-4h after dosing half of the PR dose reached the jejunum. The remaining EPN in the small intestine after oral administration(7.5 mg/kg)reached peak levels 2h after dosing, but then partly increased again at 4h. 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 reduction in gastric motility caused by the drug.
公益社団法人日本薬学会の論文
2001-07-01

Pharmacokinetics of Epinastine and a Possible Mechanism for Double Peaks in Oral Plasma Concentration Profiles

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