Regional gastrointestinal absorption of ranitidine in the rat.
OBJECTIVE
Ranitidine absorption from isolated segments of rat small intestine (duodenum, midgut, and terminal ileum) was investigated to examine the influence of pH and 50% bile, and to determine if ranitidine is absorbed preferentially from a specific region.


METHODS
Ranitidine (50 mg/kg) was administered into each segment in pH 5 or pH 7 buffer, or in 50% bile. Venous blood was collected at various times for 40 min from the right jugular vein.


RESULTS
When ranitidine was administered in pH 7 buffer or in 50% bile, Cmax and AUC0-40 were significantly greater after administration into the terminal ileum compared to the duodenum and midgut. AUC0-40 was significantly greater when ranitidine was administered in pH 5 buffer or in 50% bile into the duodenum compared to the midgut. Cmax was significantly different between administration into the duodenum and midgut only when ranitidine was administered in 50% bile. Ranitidine administration in pH 5 buffer significantly decreased AUC0-40 and Cmax after administration into the midgut, and AUC0-40 after administration into the terminal ileum compared to administration with pH 7 buffer or in 50% bile. Bile had no significant effect on AUC0-40 after ranitidine administration into the duodenum and midgut compared to administration in pH 7 buffer. However, bile significantly increased AUC0-40 and Cmax after ranitidine administration into the terminal ileum compared to administration with pH 7 and pH 5 buffer.


CONCLUSIONS
Results suggest that ranitidine is absorbed from the entire small intestine. However, the terminal ileum is the optimal site of gastrointestinal absorption. Furthermore, bile enhances ranitidine absorption from the terminal ileum.
Suttle
A B
AB
Zeneca Pharmaceutials, Wilmington, DE, USA.
Brouwer
K L
KL
D000818:Animals; D001646:Bile / Q000378:metabolism; D004386:Duodenum / Q000378:metabolism; D006635:Histamine H2 Antagonists / Q000493:pharmacokinetics*; D006863:Hydrogen-Ion Concentration; D007082:Ileum / Q000378:metabolism; D066298:In Vitro Techniques; D007408:Intestinal Absorption / Q000502:physiology*; D008297:Male; D011899:Ranitidine / Q000097:blood / Q000493:pharmacokinetics*; D051381:Rats; D017207:Rats, Sprague-Dawley; D014018:Tissue Distribution
D006635:Histamine H2 Antagonists; D011899:Ranitidine