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 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 Cmax was reached 2 h 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 14C-EPN, which has already been 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 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 3-4 h 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 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 reduction in gastric motility caused by the drug.
Ogiso
T
T
Faculty of Pharmaceutical Sciences, Kinki University, Higashi-Osaka, Osaka, Japan.
Kasutani
M
M
Tanaka
H
H
Iwaki
M
M
Tanino
T
T
D000284:Administration, Oral; D000465:Algorithms; D000818:Animals; D001646:Bile / Q000378:metabolism; D003984:Dibenzazepines / Q000097:blood / Q000493:pharmacokinetics*; D004764:Enterohepatic Circulation; D005772:Gastrointestinal Transit; D006634:Histamine H1 Antagonists / Q000097:blood / Q000493:pharmacokinetics*; D007093:Imidazoles / Q000097:blood / Q000493:pharmacokinetics*; D007202:Indicators and Reagents; D007275:Injections, Intravenous; D007421:Intestine, Small / Q000378:metabolism; D008297:Male; D010637:Phenolsulfonphthalein; D051381:Rats; D017208:Rats, Wistar
D003984:Dibenzazepines; D006634:Histamine H1 Antagonists; D007093:Imidazoles; D007202:Indicators and Reagents; D010637:Phenolsulfonphthalein; C053090:epinastine