Measurement of drug concentration in the stomach after intragastric administration of drug solution to healthy volunteers: analysis of intragastric fluid dynamics and drug absorption

Pharm Res. 2013 Apr;30(4):951-8. doi: 10.1007/s11095-012-0931-1. Epub 2012 Nov 21.

Abstract

Purpose: To evaluate the time-profile of intragastric fluid volume in humans after intragastric administration of drug solution.

Methods: Eight healthy volunteers were intragastrically administered 150 mL of drug solution containing atenolol (non-absorbable marker) and salicylic acid, then, aliquots of gastric fluid (ca. 2 mL) were sampled for 2 h through the catheter. Rate constants for secretion and emptying of the fluid were obtained by fitting the time-course of atenolol concentration to the simple gastric fluid transit model. Absorption of salicylic acid from the stomach was estimated by comparing its gastric concentration with that of atenolol.

Results: Kinetic analysis of atenolol concentration in the stomach indicated a rapid emptying of the fluid with an average half-life of 4.2 min. Steady-state intragastric fluid volume in 8 volunteers was estimated as 4-133 mL with an average of 42 mL. Intragastric concentration (normalized by dose) of salicylic acid was always lower than that of atenolol, showing approximately 40% of salicylic acid was absorbed from the stomach before emptying to the intestine.

Conclusions: This study provided valuable information on intragastric fluid dynamics and gastric drug absorption in humans to establish a better in vitro-in vivo correlation in oral drug absorption.

Publication types

  • Clinical Trial

MeSH terms

  • Adult
  • Atenolol / administration & dosage
  • Atenolol / pharmacokinetics*
  • Gastric Emptying*
  • Half-Life
  • Humans
  • Hydrodynamics
  • Hydrogen-Ion Concentration
  • Intestinal Absorption*
  • Kinetics
  • Male
  • Salicylic Acid / administration & dosage
  • Salicylic Acid / pharmacokinetics*
  • Stomach / physiology*
  • Young Adult

Substances

  • Atenolol
  • Salicylic Acid