Vw. Steinijans et al., LACK OF PANTOPRAZOLE DRUG-INTERACTIONS IN MAN, International journal of clinical pharmacology and therapeutics, 32(8), 1994, pp. 385-399
This review summarizes the results of pharmacokinetic and pharmacodyna
mic drug interaction studies in man with pantoprazole, a new, selectiv
e proton pump inhibitor. Different mechanisms have to be considered as
causes for potential drug-drug interactions. Proton pump inhibitors (
PPIs) in general may alter the absorption of drugs by increasing the i
ntragastric pH. Due to the presence of an imidazole ring, the PPIs of
the class of substituted benzimidazole sulfoxides may interfere with t
he metabolism of other drugs by altering the activity of drug metaboli
zing enzymes of the cytochrome P450 system, via either induction or in
hibition. With the increasing use of PPIs, their interaction potential
gains therapeutic importance as was the case with the first and secon
d generation of H-2-blockers (cimetidine and ranitidine, respectively)
. The enhanced selectivity of pantoprazole to the gastric H+/K+-ATPase
characterizes the new PPI generation. In comparison to omeprazole and
lansoprazole, pantoprazole showed a much lower affinity to cytochrome
P450 in vitro and a markedly lower potency in the in vivo rat model f
or interaction with diazepam In contrast to omeprazole, pantoprazole d
oes not interact with the cytochrome P450 system in man. In the drug i
nteraction studies conducted so far, pantoprazole did not affect the p
harmacokinetics or pharmacodynamics of antipyrine, diazepam, digoxin,
a hormonal contraceptive, nifedipine, phenytoin, theophylline and warf
arin in man. Also pantoprazole neither induced the drug metabolism of
antipyrine nor increased urinary excretion of the induction markers D-
glucaric acid and 6 beta-hydroxycortisol. Vice versa, the investigated
drugs had no relevant influence on the pharmacokinetics of pantoprazo
le.