The sugar absorption test in the evaluation of the gastrointestinal intolerance to bisphosphonates: Studies with oral pamidronate

Rationale and aim: Some bisphosphonates induce gastrointestinal side effect s, but the localization in the gastrointestinal tract and the underlying me chanism are unknown. The feasibility of the sugar absorption test was inves tigated to assess the gastrointestinal effects of oral enteric-coated pamid ronate. The sugar absorption test measures the urinary excretion of lactulo se, mannitol, and sucrose after oral intake. Increases in the lactulose/man nitol ratio and sucrose excretion indicate increased small intestinal perme ability and gastroduodenal disease, respectively. Subjects and methods: Twelve volunteers (5 women and 7 men) participated in a randomized, double-blind, 4-way crossover study. The sugar absorption te st was performed 2 hours after the final drug intake following a 3-day cour se of enteric-coated pamidronate (300 mg daily), placebo, or acetylsalicyli c acid (3 g daily). The lactulose/mannitol ratio and sucrose excretion were measured in urine collected for 5 hours after ingestion of the solution. T he fourth treatment consisted of intravenous administration of pamidronate. Treatment comparison was with paired t tests after log-transformation. Results: The lactulose/mannitol ratio after pamidronate and acetylsalicylic acid administration was 54% and 118% higher than that after placebo (95% c onfidence intervals [CI], +8%, +119%, and +69%, +182%). The lactulose/manni tol ratio after pamidronate administration was 29% lower (95% CI, -54%, +3% ) than that after acetylsalicylic acid. Compared with placebo the sucrose e xcretion was 290% higher after acetylsalicylic acid (95% CI, +46%, +518%) b ut only 8% higher after pamidronate (95% CI, -41%, +97%). The absorption of pamidronate was below 1%, and there was no relationship with the increased lactulose/mannitol ratio. Conclusion: Oral enteric-coated pamidronate increases intestinal but not ga stroduodenal permeability. There was no relationship between intestinal per meability and absorption of pamidronate. It appears that the sugar absorpti on test is an appropriate, noninvasive method for evaluation of gastrointes tinal effects of bisphosphonates in humans.