Gastrointestinal transit and distribution of ranitidine in the rat.
OBJECTIVE
Ranitidine gastrointestinal distribution was examined in the rat small intestine after oral administration to determine whether intestinal transit or secretion (exsorption) may influence the appearance of secondary peaks in ranitidine serum concentration-time profiles.


METHODS
Male Sprague-Dawley rats received ranitidine (50 mg/kg) by oral gavage, and the mass of ranitidine recovered in all small intestinal segments (approximately 12 cm each) was determined 30, 60, 90, or 120 min after administration. In a separate group of anesthetized rats, the small intestine was divided into two segments of equal length that were perfused with normal saline in a single-pass manner. Rats received an escalating, zero-order IV infusion of ranitidine for 30 min, and venous blood and intestinal effluent were collected over 90 min to quantitate ranitidine exsorption.


RESULTS
Thirty min after oral administration, > 50% of the recovered ranitidine mass resided in the lower half of the small intestine in all rats. Ranitidine mass in 5 of 16 rats displayed a bimodal distribution with significant amounts of ranitidine recovered from the stomach 60 to 90 min after dosing. Ranitidine exsorption was more efficient from the lower jejunum and ileum than from the duodenum and upper jejunum. However, intestinal secretion of ranitidine was minor (5% of the IV dose).


CONCLUSIONS
Ranitidine absorption from the lower ileum contributes significantly to systemic ranitidine concentrations before and during the time of the first concentration maximum. Separation of the drug mass into multiple boluses may contribute to secondary peaks in ranitidine concentration-time profiles. Exsorption did not contribute significantly to ranitidine distribution in the gastrointestinal tract.
Suttle
A B
AB
Zeneca Pharmaceuticals, Wilmington, DE, USA.
Brouwer
K L
KL
D000818:Animals; D004064:Digestive System / Q000378:metabolism*; D005772:Gastrointestinal Transit / Q000502:physiology*; D006635:Histamine H2 Antagonists / Q000097:blood / Q000493:pharmacokinetics*; D007408:Intestinal Absorption / Q000502:physiology; D008297:Male; D011899:Ranitidine / Q000097:blood / Q000493:pharmacokinetics*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013997:Time Factors; D014018:Tissue Distribution
D006635:Histamine H2 Antagonists; D011899:Ranitidine