Article date: May 1992
By: CH Wilder‐Smith, F Halter, W Hacki, HS Merki, in Volume 33, Issue 5, pages 487-493
1. The antisecretory responses to pH‐feedback controlled (maximum dose 800 mg 24 h‐1) and fixed‐dose (0.25 mg kg‐1 h‐1) continuous infusions of ranitidine were compared in a randomised, placebo‐controlled, cross‐ over study in 10 healthy male volunteers. 2. To assess tolerance during repeated dosing with ranitidine, the same infusion regimens were given before and after 6 days oral dosing with ranitidine 300 mg four times daily. 3. With the pH‐feedback controlled infusion of ranitidine the median % time (interquartile range) with pH greater than 4 in the 24 h period was 57% (45‐76) before and 23% (17‐34) after 6 days oral dosing (P less than 0.001). The respective values with fixed‐dose infusion were 51% (38‐63) and 26% (15‐32) (P less than 0.002). 4. The median 24 h doses (interquartile range) of ranitidine given by feedback‐ controlled infusion before and after 6 days oral dosing were 675 mg (542‐728) and 749 mg (709‐760), respectively (P less than 0.01). The dose of ranitidine given by fixed‐rate infusion was 423 mg (393‐502) on both study days (P less than 0.001 vs feedback infusion). 5. Plasma gastrin concentrations remained slightly elevated after 6 days of oral ranitidine dosing, whereas pancreatic polypeptide plasma levels remained unchanged. 6. The antisecretory efficacy of infusions of ranitidine is significantly decreased by circadian stimuli and tolerance. Individually‐adapted infusions of high doses of ranitidine were not superior to fixed‐dose infusion of 0.25 mg kg‐1 h‐1 in overcoming this variability.
DOI: 10.1111/j.1365-2125.1992.tb04075.x
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