Prediction of plasma concentration-time curve of orally administered theophylline based on a scintigraphic monitoring of gastrointestinal transit in human volunteers

Shunji Haruta, Keiichi Kawai, Ryuichi Nishii, Seishi Jinnouchi, Ken Ichi Ogawara, Kazutaka Higaki, Shozo Tamura, Kazuhiko Arimori, Toshikiro Kimura

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The plasma concentration-time profile of theophylline after oral administration in human volunteers was predicted using the individual gastrointestinal (GI) transit data monitored by a gamma scintigraphic technique. Theophylline was administered as aminophylline under fasted and fed condition, along with 99mTc-labeled diethylenetriamine-pentaacetic acid (DTPA), an unabsorbable marker to evaluate the GI transit by a gamma scintigraphic technique. Two healthy male volunteers participated under fasted and fed conditions in a crossover study. The GI transit was evaluated by dividing the GI tract to four segments, stomach, jejunum, ileum and cecum/colon. Under the fed condition, the GI transit pattern for each segment was confirmed to alter considerably, causing a delay in the gastric emptying mainly. Further, the plasma concentration curves of theophylline after oral administration were predicted using the GI-Transit-Absorption Model on the basis of individual GI transit parameters calculated by the fitting of the observed data to the GI-Transit Kinetic Model. The absorption rate constant in each segment and the pharmacokinetic parameters after intravenous administration used for the prediction were the values extrapolated from the data in rats and the ones normalized from the values in literatures, respectively. The plasma concentration-time curves for theophylline were well predicted using obtained individual GI transit parameters. The analysis using this method could estimate the variable absorption behavior governed by the GI transit in detail.

Original languageEnglish
Pages (from-to)179-190
Number of pages12
JournalInternational Journal of Pharmaceutics
Issue number1-2
Publication statusPublished - Feb 21 2002



  • Gamma scintigraphy
  • Gastrointestinal transit
  • GI-transit-absorption model
  • Human
  • Oral absorption
  • Prediction of absorption profile

ASJC Scopus subject areas

  • Pharmaceutical Science

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