Evaluation of absorption kinetics of orally administered theophylline in rats based on gastrointestinal transit monitoring by gamma scintigraphy

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

Research output: Contribution to journalArticle

29 Citations (Scopus)

Abstract

The gastrointestinal (GI) transit and absorption of orally administered theophylline, a highly absorbable drug without presystemic elimination, were investigated under fasted and fed conditions using three rats in a crossover study. To evaluate the GI transit rate for each segment in vivo, a noninvasive technique, gamma scintigraphy, was employed using a nonabsorbable compound, 99mTc-labeled diethylenetriamine pentaacetic acid (DTPA). Using a gamma scintigraphic technique it is possible to simultaneously evaluate the GI transit and absorption of orally administered drug in the same individual. Theophylline was simultaneously administered along with [99mTc]DTPA to animals in the fasted and fed states. Each GI transit pattern, simulated using the GI transit-kinetic model with a lag time factor, was well fitted to the experimental data. Gastric emptying rate varied in each study, even under the same experimental condition. The GI transit pattern for each segment was highly variable, especially in animals in the fed state. This inconsistency in transit pattern was mainly due to the variability in gastric emptying, which was much slower in animals in the fed compared with the fasted state. However, in spite of a large variability of GI transit kinetics, the plasma concentration-time curves of theophylline were well predicted by the GI transit-absorption model using the individual GI transit parameters obtained in the study. The absorption rate of theophylline was considerably reduced in animals in the fed state, because of the reduction of gastric emptying rate. Analysis using GI transit-absorption model and gamma scintigraphic technique made it possible to estimate the variable absorption kinetics regulated by GI transit with huge variability.

Original languageEnglish
Pages (from-to)464-473
Number of pages10
JournalJournal of Pharmaceutical Sciences
Volume90
Issue number4
DOIs
Publication statusPublished - 2001

Fingerprint

Gastrointestinal Transit
Theophylline
Radionuclide Imaging
Rats
Animals
Pentetic Acid
Kinetics
Monitoring
Gastric Emptying
Pharmaceutical Preparations
Plasmas
Cross-Over Studies

Keywords

  • Gamma scintigraphy
  • Gastrointestinal transit
  • GI transit absorption model
  • Oral absorption kinetics
  • Theophylline

ASJC Scopus subject areas

  • Drug Discovery
  • Organic Chemistry
  • Chemistry(all)
  • Molecular Medicine
  • Pharmacology
  • Pharmaceutical Science

Cite this

Evaluation of absorption kinetics of orally administered theophylline in rats based on gastrointestinal transit monitoring by gamma scintigraphy. / Haruta, Shunji; Kawai, Keiichi; Jinnouchi, Seishi; Ogawara, Ken Ichi; Higaki, Kazutaka; Tamura, Shozo; Arimori, Kazuhiko; Kimura, Toshikiro.

In: Journal of Pharmaceutical Sciences, Vol. 90, No. 4, 2001, p. 464-473.

Research output: Contribution to journalArticle

Haruta, Shunji ; Kawai, Keiichi ; Jinnouchi, Seishi ; Ogawara, Ken Ichi ; Higaki, Kazutaka ; Tamura, Shozo ; Arimori, Kazuhiko ; Kimura, Toshikiro. / Evaluation of absorption kinetics of orally administered theophylline in rats based on gastrointestinal transit monitoring by gamma scintigraphy. In: Journal of Pharmaceutical Sciences. 2001 ; Vol. 90, No. 4. pp. 464-473.
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