Influence of polyethylene glycol 400 on the gastrointestinal absorption of ranitidine.
OBJECTIVE
To investigate the effect of co-administered polyethylene glycol 400 (PEG 400), a pharmaceutical excipient previously shown to accelerate small intestinal transit, on the absorption characteristics of ranitidine from the gastrointestinal tract.


METHODS
Ten healthy male volunteers each received, on two separate occasions, an immediate-release pellet formulation of ranitidine (150 mg) encapsulated within a hard gelatin capsule and a liquid preparation consisting of 150 ml orange juice (control) or 150 ml orange juice containing 10 g PEG 400 (test). The liquid preparations were also radiolabelled with indium-III to allow their transit through the gastrointestinal tract to be followed using a gamma camera. On a further occasion an intravenous injection of ranitidine (50 mg) was administered. Blood samples were taken over a 12 h period on each study day to allow a ranitidine plasma and subsequent absorption rate profile to be generated for each oral formulation. Urine was collected for 24 h and assessed for PEG 400 concentration.


RESULTS
The absolute bioavailability of ranitidine from the pellet formulation was significantly reduced by 31% (from 51% to 35%) and small intestinal liquid transit time was significantly shortened by 37% (from 226 min to 143 min) as a consequence of PEG 400 in the test preparation. PEG 400 also affected the rate of ranitidine absorption, with major differences noted in the mean absorption time and Cmax parameters. The appearance of double peaks were less evident in the ranitidine pharmacokinetic profiles in the presence of PEG 400, and little or no correlation was observed between the absorption of ranitidine and PEG 400.


CONCLUSIONS
These results clearly demonstrate that PEG 400 adversely influences the gastrointestinal absorption of ranitidine. This in turn has ramifications for the use of PEG 400 as a pharmaceutical excipient in oral formulations.
Basit
Abdul W
AW
Department of Pharmaceutics, The School of Pharmacy, University of London, United Kingdom. abdul.basit@ulsop.ac.uk
Podczeck
Fridrun
F
Newton
J Michael
JM
Waddington
Wendy A
WA
Ell
Peter J
PJ
Lacey
Larry F
LF
D001682:Biological Availability; D018592:Cross-Over Studies; D004064:Digestive System / Q000187:drug effects / Q000378:metabolism; D004347:Drug Interactions / Q000502:physiology; D006801:Humans; D007408:Intestinal Absorption / Q000187:drug effects / Q000502:physiology*; D008297:Male; D011092:Polyethylene Glycols / Q000493:pharmacokinetics* / Q000494:pharmacology; D011899:Ranitidine / Q000097:blood / Q000493:pharmacokinetics*
D011092:Polyethylene Glycols; D011899:Ranitidine