title: Appearance of double peaks in plasma concentration-time profile after oral administration depends on gastric emptying profile and weight function.
abstract: OBJECTIVE
  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.
  
  
  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.
authors.affiliation: Department of Pharmaceutics, Faculty of Pharmaceutical Sciences, Okayama University, 1-1-1 Tsushima-naka, Okayama, 700-8530, Japan.
authors.forename: Yukiko
authors.initials: Y
authors.lastname: Metsugi
authors.forename: Yoshihiro
authors.initials: Y
authors.lastname: Miyaji
authors.forename: Ken-ichi
authors.initials: K
authors.lastname: Ogawara
authors.forename: Kazutaka
authors.initials: K
authors.lastname: Higaki
authors.forename: Toshikiro
authors.initials: T
authors.lastname: Kimura
mesh_terms: D000284:Administration, Oral; D000525:Alprazolam / Q000008:administration & dosage* / Q000097:blood / Q000493:pharmacokinetics*; D000818:Animals; D003198:Computer Simulation; D005746:Gastric Emptying / Q000187:drug effects*; D007408:Intestinal Absorption / Q000187:drug effects*; D008297:Male; D008657:Metabolic Clearance Rate; D008954:Models, Biological; D051381:Rats; D017208:Rats, Wistar; D013806:Theophylline / Q000008:administration & dosage* / Q000097:blood / Q000493:pharmacokinetics*
chemical_list: D013806:Theophylline; D000525:Alprazolam