Drug marker absorption in relation to pellet size, gastric motility and viscous meals in humans

Julie K. Rhie, Yayoi Hayashi, Lynda S. Welage, Jeremy Frens, Randy J. Wald, Jeffrey L. Barnett, Gregory E. Amidon, Lakshmi Putcha, Gordon L. Amidon

Research output: Contribution to journalArticlepeer-review

24 Scopus citations

Abstract

Purpose. The objective of this study was to evaluate drug marker absorption in relation to the gastric emptying (GE) of 0.7 mm and 3.6 mm enteric coated pellets as a function of viscosity and the underlying gastric motility. Methods. Twelve subjects were evaluated in a 3-way crossover study. 0.7 mm caffeine and 3.6 mm acetaminophen enteric coated pellets were concurrently administered with a viscous caloric meal at the levels of 4000, 6000 and 8000 cP. Gastric motility was simultaneously measured with antral manometry and compared to time events in the plasma profiles of the drug markers. Results. Caffeine, from the 0.7 mm pellets, was observed significantly earlier in the plasma than acetaminophen, from the 3.6 mm pellets, at all levels of viscosity. Motility related size differentiated GE was consistently observed at all viscosity levels, however, less variability was observed with the 4000 cP meal. 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 interaction between viscosity and motility influencing antral flow dynamics. The administration of the two sizes of pellets and a viscous caloric meal with subsequent monitoring of drug marker profiles is useful as a reference to assess the influence of motility patterns on the absorption profile of orally administered agents.

Original languageEnglish (US)
Pages (from-to)233-238
Number of pages6
JournalPharmaceutical research
Volume15
Issue number2
DOIs
StatePublished - 1998

Keywords

  • Acetaminophen
  • Caffeine
  • Enteric coated
  • Gastric emptying
  • Gastric motility
  • Oral absorption
  • Viscous meal

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