Oral Biodisposition Study of Ritodrine after Its Buccal Administration in Rats.

BACKGROUND: In the previous study, buccal absorption of ritodrine (RD) hydrochloride was reported in vivo. As a result, buccal dosing of RD solution was found to be useful for the maintenance of effective plasma concentration. However, in order to find out the dosing schedule more clearly, it is important to clarify the in vivo drug behavior.

OBJECTIVE: The biodistributions of RD in oral cavity and buccal mucosal were investigated in order to understand the in vivo drug behavior after the buccal application.

METHOD: The pharmacokinetic parameters for 0 - infinite time and the absorption rate were calculated based on the plasma level-time profiles in the intravenous (1 mg/kg), buccal (10 mg/kg) and intragastric (10 mg/kg) dosings using rats. The drug concentrations in buccal mucosa and the remaining drug amounts in the oral cavity were examined over time after the buccal administration. From those drug distributions and drug absorption rates, the kinetic aspects were discussed.

RESULTS: The absolute bioavailabilities of RD were 14.2% and 4.3% in buccal and intragastric (0.043) administrations, respectively. The oral cavity concentration was quickly eliminated within 0.5 h, and then decreased slowly. In both the administration site and distant region, the mucosal RD concentrations were observed at several dozen to approximately 100 μg/g during 0.5-4 h, indicating the rapid diffusion in the oral cavity. For both the mucosal parts, the buccal mucosal level reached a maximal level at 1 h, and then was slowly eliminated. The absorption rates were not related linearly to the buccal mucosal level, suggesting that the other mucosal parts such as sublingual mucosa and tongue ventral surface should be involved considerably in the absorption.

CONCLUSION: The changes in RD concentration in oral cavity and oral mucosa showed the drug behavior in vivo. The present study revealed that RD is not accumulated in the buccal mucosa and transfers relatively fast from the oral mucosa to systemic circulation. It was suggested that the buccal dosing of RD should be acceptable even in the repeated manner as an alternative to the intravenous or oral administration of RD.