Concentration-dependent effects of polyethylene glycol 400 on gastrointestinal transit and drug absorption.
OBJECTIVE
The aim of the study was to investigate the effect of different concentrations of polyethylene glycol 400 (PEG 400) on liquid transit through, and ranitidine absorption from, the gastrointestinal tract.


METHODS
Six healthy male volunteers received, on four separate occasions, 150 mL water containing 150 mg ranitidine and either 0 (control), 1,2.5, or 5 g PEG 400. The solutions were radiolabeled with technetium-99m to allow their gastrointestinal transit to be followed using a gamma camera. Urine samples were collected over a 24-h period to assess the amount of ranitidine excreted and hence absorbed.


RESULTS
No significant differences in gastric emptying were noted between the four solutions. In contrast, the presence of 1, 2.5, and 5 g PEG 400 reduced the mean small intestinal transit times of the solutions by 9, 20, and 23%, respectively, against the control. In terms of drug absorption, the mean cumulative amount of ranitidine excreted was reduced by 38% in the presence of both 2.5 and 5 g PEG 400, although it was significantly increased by 41% in the presence of 1 g PEG 400.


CONCLUSIONS
The results show that low concentrations of PEG 400 enhance the absorption of ranitidine possibly via modulation of intestinal permeability, while high concentrations have a detrimental effect on ranitidine absorption presumably via a reduction in the small intestinal transit time.
Schulze
Julia D R
JD
Department of Pharmaceutics, The School of Pharmacy, University of London, 29-39 Brunswick Square, London WC1N 1AX, UK.
Waddington
Wendy A
WA
Eli
Peter J
PJ
Parsons
Gary E
GE
Coffin
Mark D
MD
Basit
Abdul W
AW
D000328:Adult; D000897:Anti-Ulcer Agents / Q000008:administration & dosage / Q000493:pharmacokinetics; D002214:Capsules; D002432:Cecum / Q000378:metabolism; D002626:Chemistry, Pharmaceutical; D005079:Excipients; D005772:Gastrointestinal Transit / Q000187:drug effects*; D006801:Humans; D007408:Intestinal Absorption / Q000187:drug effects*; D008297:Male; D004364:Pharmaceutical Preparations / Q000378:metabolism*; D019999:Pharmaceutical Solutions; D011092:Polyethylene Glycols / Q000494:pharmacology*; D011899:Ranitidine / Q000008:administration & dosage / Q000493:pharmacokinetics
D000897:Anti-Ulcer Agents; D002214:Capsules; D005079:Excipients; D004364:Pharmaceutical Preparations; D019999:Pharmaceutical Solutions; D011092:Polyethylene Glycols; D011899:Ranitidine