Omeprazole-induced increase in the absorption of bismuth from tripotassium dicitrato bismuthate

Omeprazole is an effective drug for treating active peptic ulcer, whereas tripotassium dicitrato bismuthate can prevent ulcer relapse if Helicobacter pylori is eradicated. Because both drugs will be given concomitantly, drug interactions have to be considered, especially since absorption of bismuth may be dependent on intragastric pH, which will be elevated by omeprazole.

In a placebo-controlled crossover study, six healthy volunteers received daily oral doses of 40 mg omeprazole for 1 week and a single oral dose of 240 mg tripotassium dicitrato bismuthate. Plasma concentration-time profiles (AUC) and urinary excretion (Ae) of bismuth were measured by atomic absorption spectrophotometry and plasma levels of omeprazole by HPLC. In addition, intragastric pH values were monitored for 8 hours.

As expected, control mean pH values (2.1) were evaluated to 4.7 by omeprazole (p = 0.001), which was eliminated with a half-life of 1.3 +/- 0.7 hours (mean +/- SD) and an oral clearance of 387 +/- 221 ml/min. The increase of intragastric pH was related to the AUC of omeprazole (r = 0.89; p = 0.017). Omeprazole increased absorption of bismuth because AUC and Ae were higher (p < or = 0.05) during omeprazole treatment (172 +/- 158 micrograms/L.hr and 1.9 +/- 2.0 mg/8 hr, respectively) compared with placebo (46 +/- 33 micrograms/L.hr and 0.27 +/- 0.28 mg/8 hr, respectively). A significant correlation (r = 0.85; p = 0.038) could be observed between intragastric pH differences and Ae values.

Omeprazole caused an increase of the systemic availability of bismuth from tripotassium dicitrato bismuthate. Whether this pharmacokinetic interaction between both drugs results in alterations of H. pylori eradication or the toxic potential of bismuth remains to be elucidated by further clinical studies.