Effect of omeprazole treatment on diazepam plasma levels in slow versus normal rapid metabolizers of omeprazole

The effect of omeprazole treatment on diazepam plasma levels was studied in four slow and six rapid metabolizers of omeprazole. Single intravenous doses of diazepam (0.1 mg/kg) were administered after 1 week of oral treatment with omeprazole (20 mg) and placebo. This was a double-blind crossover study with randomized placebo and omeprazole treatments. Blood was collected up to 120 hours after diazepam dosing (still during one-daily omeprazole and placebo administration) for measurement of diazepam and its major metabolite desmethyldiazepam. The slow metabolizers of omeprazole also metabolized diazepam slowly, exhibiting only half the diazepam plasma clearance of the others. The mean clearance of diazepam was decreased 26% after omeprazole in the rapid metabolizers, whereas the slow group showed no apparent interaction. The mean plasma concentrations of desmethyldiazepam showed a more rapid formation in the rapid compared with the slow metabolizers, which is a logical consequence of the rate of diazepam metabolism.