Appearance of double peaks in plasma concentration-time profile after oral administration depends on gastric emptying profile and weight function

Yukiko Metsugi, Yoshihiro Miyaji, Ken Ichi Ogawara, Kazutaka Higaki, Toshikiro Kimura

Research output: Contribution to journalArticle

42 Citations (Scopus)

Abstract

Purpose. Mechanism for double-peak occurrence in plasma concentration profile after oral administration of drugs is controversial, although irregular gastric emptying would be an important factor. The objective of this study was to assess the effect of gastric emptying and a weight function, i.e. pharmacokinetics after reaching the systemic circulation, on the double-peak appearance in plasma concentration profiles. Materials and Methods. Alprazolam, which generates irregular gastric emptying, was orally co-administered with theophylline to rats, and the plasma concentration profiles or absorption rates were compared between the two drugs. Both drugs are highly absorbable, but alprazolam is rapidly eliminated from plasma, while the elimination of theophylline is very slow. Results. Oral administration of alprazolam generated the irregular gastric emptying profiles, resulting in multiple peaks in the absorption rate profiles of both drugs. The double peaks in the absorption rate profiles led to the double peaks in plasma concentration profiles for alprazolam, but not necessarily for theophylline. Simulation study clearly indicated that the slower elimination from plasma made the first peak less recognizable. Conclusions. The irregular gastric emptying could be a main reason for the double peaks in plasma concentration profiles. However, the frequency of double-peak occurrence depends on the weight function, particularly the elimination rate, of each drug.

Original languageEnglish
Pages (from-to)886-895
Number of pages10
JournalPharmaceutical Research
Volume25
Issue number4
DOIs
Publication statusPublished - Apr 2008

Fingerprint

Gastric Emptying
Oral Administration
Alprazolam
Plasmas
Weights and Measures
Theophylline
Pharmaceutical Preparations
Pharmacokinetics
Rats

Keywords

  • Absorption rate
  • Double peaks
  • Gastric emptying
  • Weight function

ASJC Scopus subject areas

  • Chemistry(all)
  • Pharmaceutical Science
  • Pharmacology

Cite this

Appearance of double peaks in plasma concentration-time profile after oral administration depends on gastric emptying profile and weight function. / Metsugi, Yukiko; Miyaji, Yoshihiro; Ogawara, Ken Ichi; Higaki, Kazutaka; Kimura, Toshikiro.

In: Pharmaceutical Research, Vol. 25, No. 4, 04.2008, p. 886-895.

Research output: Contribution to journalArticle

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