Vw. Steinijans et al., LACK OF PANTOPRAZOLE DRUG-INTERACTIONS IN MAN - AN UPDATED REVIEW, International journal of clinical pharmacology and therapeutics, 34, 1996, pp. 31-50
This review summarizes the results of pharmacokinetic and pharmacodyna
mic drug interaction studies in man with pantoprazole, a new, selectiv
e proton pump inhibitor. Various mechanisms have to be considered as c
auses for potential drug-drug interactions. Proton pump inhibitors (PP
Is) in general may alter the absorption of drugs by increasing the int
ragastric pH. Due to the presence of an imidazole ring, the PPIs of th
e class of substituted benzimidazole sulfoxides may interfere with the
metabolism of other drugs by altering the activity of drug metabolizi
ng enzymes of the cytochrome P450 system, via either induction or inhi
bition. With the increasing use of PPIs, their interaction potential g
ains therapeutic importance as was the case with the first and second
generation of H-2-blockers (cimetidine and ranitidine, respectively).
The enhanced selectivity of pantoprazole to the gastric H+/K+-ATPase c
haracterizes the new PPI generation. In contrast to omeprazole, pantop
razole has a low potential to interact with the cytochrome P450 system
in man. In the drug interaction studies conducted so far, substrates
for all relevant cytochrome P450 families involved in the metabolism o
f drugs in man were investigated. Pantoprazole did not affect the phar
macokinetics or pharmacodynamics of antipyrine, caffeine, carbamazepin
e, diazepam, diclofenac, digoxin, ethanol, glibenclamide, a hormonal c
ontraceptive (combination of levonorgestrel and ethinylestradiol), met
oprolol, nifedipine, phenprocoumon, phenytoin, theophylline and warfar
in in man. Pantoprazole also neither induced the metabolism of antipyr
ine or caffeine, nor increased urinary excretion of the induction mark
ers D-glucaric acid and 6 beta-hydroxycortisol. Vice versa, the invest
igated drugs had no relevant influence on the pharmacokinetics of pant
oprazole.