EFFECT OF PANCREATICOBILIARY SECRETIONS AND GI TRANSIT-TIME ON THE ABSORPTION AND PHARMACOKINETIC PROFILE OF RANITIDINE IN HUMANS

Purpose. Ranitidine plasma concentration vs. time profiles and the ext ent 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 administratio n. Methods. Ranitidine solution (300 mg) was administered to 4 fasting healthy subjects via an indwelling small-bore oroenteric tube located similar to 16 cm distal to the pylorus. On 3 consecutive days, subjec ts randomly received ranitidine alone (control), ranitidine 10 min aft er 0.04 mu g/kg IV cholecystokinin (CCK) sufficient to cause gall blad der emptying into the duodenum, and ranitidine 30 min after inflation of an occlusive duodenal balloon located similar to 10 cm distal to th e pylorus to prevent pancreatico-biliary secretions from reaching the dosing port or beyond: Small bowel transit time (SBTT: min) was measur ed by breath H-2. Serial blood samples, obtained over 12 hours in each treatment, were analyzed by HPLC to determine ranitidine AUC(0-12) (n gh/mL), as well as C-max (ng/mL) and T-max (min) of the first and sub sequent peaks, if subsequent peaks were observed. Results. Ranitidine AUC(0-12) and C-max1 were not altered significantly by treatments; tre atment effects on SBTT varied. Secondary peaks were observed in subjec ts #1 and #3 during the control treatment and subjects #2 and #4 durin g the CCK treatment. No secondary peaks were observed in any subject d uring the balloon treatment, and T-max1 was delayed. Conclusions. Resu lts support the hypothesis that pancreatico-biliary secretions (presen t in the intestinal lumen during control or CCK treatment) and gastroi ntestinal transit time may influence the occurrence of secondary peaks in ranitidine concentration vs, time profiles.