LACK OF PHARMACOKINETIC INTERACTION OF PANTOPRAZOLE WITH DIAZEPAM IN MAN

Pantoprazole, a substituted benzimidazole, is a potent and well tolera ted inhibitor of the gastric H+,K+-ATPase with a low potential to inhi bit cytochrome P450. In this randomized, placebo-controlled two-period crossover study, 12 healthy volunteers received placebo (reference) a nd 240 mg of pantoprazole (test) i.v. within 2 min once daily for 7 da ys each. On day 4 of either period, a 1 min bolus of diazepam (0.1 mg kg(-1) body weight) was additionally injected. Pantoprazole was well t olerated and did not cause clinically relevant changes in heart rate, blood pressure, ECG and routine clinical laboratory parameters. There was no effect on diazepam clearance (0.021 1 h(-1) kg(-1) for test and reference) and elimination half-life (36.8 h for test, 40.4 h for ref erence). Diazepam metabolism to desmethyldiazepam was not affected by pantoprazole. In conclusion, pantoprazole and diazepam may be administ ered concomitantly without dose adjustment even when high doses of pan toprazole are required.