Influence of Metoclopramide and Propantheline on GI Absorption of Griseofulvin in Rats

Abstract

The effect of metoclopramide and propantheline preadministration on the plasma levels of orally administered griseofulvin was studied. Griseofulvin was administered as an aqueous suspension in 0.5% polysorbate 80 or as a 100% polyethylene glycol 600 solution. Metoclopramide preadministration increased the gastric emptying rate, but propantheline retarded it. The effect on griseofulvin absorption induced by metoclopramide and propantheline was sharply dependent upon the dosage form of griseofulvin administered. When griseofulvin was administered as a suspension dosage form following metoclopramide administration, the griseofulvin peak plasma concentration was reduced by 59% while a concurrent 50% reduction in relative bioavailability was observed. Pretreatment with metoclopramide resulted in a shift of the time required for attainment of the peak plasma griseofulvin concentration. In contrast, metoclopramide administration prior to a dose of griseofulvin dissolved in 100% polyethylene glycol 600 sharply increased both the relative bioavailability and the maximum plasma level of griseofulvin by 234 and 145%, respectively. Propantheline administration prior to a single dose of griseofulvin suspension decreased the maximum plasma level by 30% and delayed the time of its attainment from 5.78 to 19.00 hr with a 50% increase in relative availability. When griseofulvin was administered as a 100% polyethylene glycol solution dosage form, propantheline preadministration reduced both the maximum plasma level and the area under the plasma concentration-time curve by 64 and 44%, respectively.