GI transit time
Springer Online Journal Archives 1860-2000
Chemistry and Pharmacology
Abstract Purpose. Ranitidine plasma concentration vs. time profiles and the extent of ranitidine absorption were examined in the presence and absence of pancreatico-biliary secretions in order to elucidate factors which may contribute to secondary peaks after oral ranitidine administration. Methods. Ranitidine solution (300 mg) was administered to 4 fasting healthy subjects via an indwelling small-bore oroenteric tube located ∼16 cm distal to the pylorus. On 3 consecutive days, subjects randomly received ranitidine alone (control), ranitidine 10 min after 0.04 μg/kg IV cholecystokinin (CCK) sufficient to cause gall bladder emptying into the duodenum, and ranitidine 30 min after inflation of an occlusive duodenal balloon located ∼10 cm distal to the pylorus to prevent pancreatico-biliary secretions from reaching the dosing port or beyond. Small bowel transit time (SBTT; min) was measured by breath H2. Serial blood samples, obtained over 12 hours in each treatment, were analyzed by HPLC to determine ranitidine AUC0−2(ng*h/mL), as well as Cmax(ng/mL) and Tmax(min) of the first and subsequent peaks, if subsequent peaks were observed. Results. Ranitidine AUC0−2and Cmax1, were not altered significantly by treatments; treatment effects on SBTT varied. Secondary peaks were observed in subjects #1 and #3 during the control treatment and subjects #2 and #4 during the CCK treatment. No secondary peaks were observed in any subject during the balloon treatment, and Tmax1was delayed. Conclusions. Results support the hypothesis that pancreatico-biliary secretions (present in the intestinal lumen during control or CCK treatment) and gastrointestinal transit time may influence the occurrence of secondary peaks in ranitidine concentration vs. time profiles.
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