THE EFFECT OF OMEPRAZOLE ON THE PHARMACOKINETICS OF METRONIDAZOLE ANDHYDROXYMETRONIDAZOLE IN HUMAN PLASMA, SALIVA AND GASTRIC-JUICE

Aims To evaluate the effect of omeprazole on the pharmacokinetics of m etronidazole and hydroxymetronidazole in plasma, gastric juice and sal iva following intravenous infusion or oral dosing of metronidazole. Me thods Eight volunteers received single doses of metronidazole (400 mg) intravenously and orally, whilst taking placebo or omeprazole (40 mg, twice daily for 5 days) in a randomized dr-way crossover study. Metro nidazole and hydroxymetronidazole concentrations in plasma, saliva and gastric juice samples were determined by h.p.l.c. Pharmacokinetic par ameters for metronidazole and hydroxymetronidazole were calculated, an d the significance of the mean differences in parameters between omepr azole and placebo co-administration was assessed using a two-tailed, p aired t-test. Results There were no significant differences (P<0.05) i n any of the plasma or saliva pharmacokinetic parameter values for met ronidazole between volunteers receiving omeprazole or placebo when met ronidazole was administered either as an intravenous infusion or orall y. Following intravenous administration of metronidazole to the placeb o group and omeprazole treated group respectively, the gastric transfe r of metronidazole was significantly reduced from 15.5 +/- 10.4% to 2. 6+/-1.0% of the dose (P= 0.007; 95% CI of difference 4.8 to 21.0) with concomitant changes in the metronidazole AUC (from 77.5 +/- 18.0 mu m ol l(-1) h to 352.6 +/- 182.1 mu mol l(-1) h; P=0.0003; 95% CI of diff erence 127.6 to 422.7), C-max (from 61.4 +/- 26.5 mu mol l(-1) to 271. 8 +/- 104.3 mu mol l(-1); P=0.0001; 95% CI of difference 118.6 to 302. 1). Similarly, the gastric juice AUC of hydroxymetronidazole was signi ficantly reduced from 3.2 +/- 1.9 mu mol l(-1) h to 1.5 +/- 0.8 mu mol l(-1) h of the dose (P= 0.0043; 95% CI of difference 0.4 to 3.0) with a concomitant change in C-max (from 5.0+/-2.5 mu mol l(-1) to 3.0 +/- 1.2 mu mol l(-1); P= 0.0007; 95% CI of difference 0.7 to 3.4). Conclu sions Omeprazole had little effect on the plasma and salivary pharmaco kinetics of metronidazole (or its hydroxymetabolite) after intravenous or oral administration, but it did have a substantial effect on the p harmacokinetics of metronidazole and hydroxymetronidazole in gastric j uice.