Variability in cimetidine absorption and plasma double peaks following oral administration in the fasted state in humans: Correlation with antral gastric motility

Narushi Takamatsu, Lynda S. Welage, Yayoi Hayashi, Ryuzo Yamamoto, Jeffrey L. Barnett, Vinod P. Shah, Lawrence J. Lesko, Chandrasekharan Ramachandran, Gordon L. Amidon

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40 Scopus citations


The role of gastrointestinal motility and pH in determining cimetidine bioavailability as well as double peaks in plasma profiles following oral administration, in the quiescent or active phase of antral motility, to humans in the fasted state was examined. Plasma cimetidine-time curves did not show the presence of double peaks in any subject following intravenous administration. The incidence of double peaks was 73% following oral administration and was independent of antral migrating motility complex phase. Further, it was found that oral administration of cimetidine in the quiescent phase resulted in significantly higher bioavailability and in other pharmacokinetic parameters compared to that obtained following administration in the active phase. Excellent linearity in plots of motility peaks vs. plasma peaks with slopes close to unity were evident for both quiescent (r2=0.93) and active phase (r2=0.97) administration. A total of 14 peaks out of 22 (10 subjects, 64%) and 20 out of 27 peaks (11 subjects, 74%), were accounted for in quiescent and active phase oral administration, respectively. The proximal occurrence of plasma peaks to antral motility peaks typical of phase III contractions strongly implies that motility patterns may be responsible for secondary maxima following oral cimetidine administration in the fasted state.

Original languageEnglish (US)
Pages (from-to)37-47
Number of pages11
JournalEuropean Journal of Pharmaceutics and Biopharmaceutics
Issue number1
StatePublished - 2002

Bibliographical note

Funding Information:
This work was supported in part by FDA Grant FD01462 and the General Clinical Research Center (GCRC) at the University of Michigan, funded by a grant (M01RR00042) from the National Center for Research Resources, National Institutes of Health, USPHS. We thank the nurses at the General Clinical Research Center and the staff of the Gastrointestinal Physiology Laboratory, at the University of Michigan Medical Center for their support and assistance with this project. We also thank John Wlodyga for his valuable assistance in various phases of this study.


  • Antral motility phase
  • Cimetidine
  • Double peaks
  • Gastrointestinal motility
  • Gastrointestinal pH
  • Human bioavailability
  • Pharmacokinetics
  • Secondary maxima


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