DRUG MARKER ABSORPTION IN RELATION TO PELLET SIZE, GASTRIC-MOTILITY AND VISCOUS MEALS IN HUMANS

Purpose. The objective of this study was to evaluate drug marker absor ption in relation to the gastric emptying (GE) of 0.7 mm and 3.6 mm en teric coated pellets as a function of viscosity and the underlying gas tric motility. Methods. Twelve subjects were evaluated in a 3-way cros sover study. 0.7 mm caffeine and 3.6 mm acetaminophen enteric coated p ellets were concurrently administered with a viscous caloric meal at t he levels of 4000, 6000 and 8000 cP. Gastric motility was simultaneous ly measured with antral manometry and compared to time events in the p lasma profiles of the drug markers. Results. Caffeine, from the 0.7 mm pellets, was observed significantly earlier in the plasma than acetam inophen, from the 3.6 mm pellets, at all levels of viscosity. Motility related size differentiated GE was consistently observed at all visco sity levels, however, less variability was observed with the 4000 cP m eal. Specifically, the onset of absorption from the of 3.6 mm pellets correlated with the onset of Phase II fasted state contractions (r = 0 .929, p < 0.01). Conclusions, The timeframe of drug marker absorption and the onset of motility events were not altered within the range of viscosities evaluated. Rather, the differences in drug marker profiles from the non-digestible solids were most likely the result of the int eraction between viscosity and motility influencing antral flow dynami cs. The administration of the two sizes of pellets and a viscous calor ic meal with subsequent monitoring of drug marker profiles is useful a s a reference to assess the influence of motility patterns on the abso rption profile of orally administered agents.