Analysis and Prediction of Absorption Behavior for Theophylline Orally Administered as Powders Based on Gastrointestinal-transit-Absorption (Gita) Model

Keitaro Kadono, Jun ichi Yokoe, Ken ichi Ogawara, Kazutaka Higaki, Toshikiro Kimura

Research output: Contribution to journalArticle

14 Citations (Scopus)

Abstract

Absorption behavior of theophylline, categorized into Class I of Biopharmaceutics Classiôcation System, orally administered as powders in rats was analyzed and predicted by Gastrointestinal-Transit-Absorption (GITA) model, which was modiôed to describe GI-transit kinetics and dissolution of powders orally administered. First of all, GI-transit kinetics of glass beads was examined to describe the transit kinetics of powders through GI tract in rats. The results showed that the gastric emptying of glass beads was slower than that of solution, but that there was not much diference in the transit rate constants through the small intestine and cecum between glass beads and solution. Furthermore, to introduce the dissolution process of theophylline powders into GITA model, an in-vitro dissolution test was examined for theophylline powders according to the Japanese Pharmacopoeia paddle method. The dissolution rate constants calculated based on the mean dissolution time were not so diferent in the range of pH from 1.2 to 6.5. Using the parameters for GI transit, dissolution and absorption obtained, the plasma concentration-time proôle of theophylline after oral administration as powders to rats was predicted based on GITA model. The proôle calculated was significantly correlated with the observed time course of plasma concentration for theophylline, and the parameters such as Cmax and AUC based on the predicted curve coincided with those on the observed data, showing that GITA model is useful for the prediction of the absorption behavior of drugs administered as powders. The simulation studies showed that about 80z of orally administered theophylline powders dissolved in the stomach and that the remaining powders rapidly moved to the lower jejunum and ileum, where they dissolved. Furthermore, it was suggested that theophylline is absorbed mostly in the upper small intestine, duodenum, upper jejunum and lower jejunum, after its oral administration as powders.

Original languageEnglish
Pages (from-to)307-315
Number of pages9
JournalDrug Metabolism and Pharmacokinetics
Volume17
Issue number4
DOIs
Publication statusPublished - 2002

Keywords

  • biopharmaceutics classiôcation system class I
  • gastrointestinal-transit-absorption (GITA) model
  • oral absorption
  • powder
  • prediction
  • theophylline

ASJC Scopus subject areas

  • Pharmacology
  • Pharmaceutical Science
  • Pharmacology (medical)

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