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Effect of Pancreatico-Biliary Secretions and GI Transit Time on the Absorption and Pharmacokinetic Profile of Ranitidine in Humans

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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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Authors and Affiliations

  1. Division of Pharmaceutics, School of Pharmacy, The University of North Carolina at Chapel Hill, C.B. 7360, Chapel Hill, North Carolina, 27599-7360

    Kellie S. Reynolds (Beard Hall), Min H. Song & Kim L. R. Brouwer

  2. Department of Gastroenterology, School of Medicine, University of North Carolina, USA

    William D. Heizer

  3. Department of Radiology, University of North Carolina Hospitals, USA

    Charles B. Burns

  4. Division of Clinical Pharmacology and Hypertension, Medical College of Virginia, USA

    Domenic A. Sica

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  1. Kellie S. Reynolds
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  2. Min H. Song
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  3. William D. Heizer
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  4. Charles B. Burns
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  5. Domenic A. Sica
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  6. Kim L. R. Brouwer
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Reynolds, K.S., Song, M.H., Heizer, W.D. et al. Effect of Pancreatico-Biliary Secretions and GI Transit Time on the Absorption and Pharmacokinetic Profile of Ranitidine in Humans. Pharm Res 15, 1281–1285 (1998). https://doi.org/10.1023/A:1011908412058

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