Pantoprazole

Pantoprazole is an inhibitor of H+/K+-ATPase [1].

Pantoprazole inhibits the activity of H+/K+-ATPase proton pumb in the parietal cells of gastric mucosa. This inhibition affects the acid secretion and thus, pantoprazole are used as drugs for the treatment of various acid-related disorders. Pantoprazole is activated slowly. The activated sulfonamide of pantoprazole binds to Cys813 and Cys822 of the pumb and inhibits acid secretion selectively. Pantoprazole inhibited lysosomal acidification with IC50 value of 194 μM. The pKa values of pantoprazole are 3.83 (pKa1) and 0.11 (pKa2). Besides that, pantoprazole also shows antibacterial effects on Helicobacter pylori [1, 2].

References:
[1] Jungnickel P W.  Pantoprazole: a new proton pump inhibitor. Clinical therapeutics, 2000, 22(11): 1268-1293.
[2] Sachs G, Shin J M, Howden C W.  Review article: the clinical pharmacology of proton pump inhibitors. Alimentary pharmacology & therapeutics, 2006, 23(s2): 2-8.

The effect of short-term oral treatment with omeprazole or pantoprazole on the function of polymorphonuclear neutrophils.[Pubmed:28177671]

Can J Physiol Pharmacol. 2017 Jun;95(6):675-680.

Recent studies report an increased risk of enteric infections in patients treated with proton pump inhibitors (PPIs). Polymorphonuclear neutrophils (PMNs) play a key role in host response to bacterial infection. We evaluated the effect of omeprazole and Pantoprazole treatment on the PMN function. Fifteen patients were treated with omeprazole 20 mg daily and 15 patients with Pantoprazole 40 mg daily for 7 days. Treatment with omeprazole or Pantoprazole had no effect on spontaneous nitroblue tetrazolium (NBT) test results. Significant increase in the percentage of phagocytes in the omeprazole group in stimulated NBT test (by 69%) was found. Treatment with omeprazole or Pantoprazole had no effect on nitric oxide (NO) concentration in the PMN culture supernatant and serum, cyclic guanosine monophosphate concentration in the PMN culture supernatant and serum, as well as inducible nitric oxide synthase (iNOS) protein expression and p38 mitogen-activated protein kinase activity in PMNs. In conclusion, treatment with PPI has no effect on NO production and p38 mitogen-activated protein kinase activity in PMNs. Interestingly, short-term treatment with omeprazole but not with Pantoprazole enhances PMN reactive oxygen species production.

A chiral LC-MS/MS method for the enantioselective determination of R-(+)- and S-(-)-pantoprazole in human plasma and its application to a pharmacokinetic study of S-(-)-pantoprazole sodium injection.[Pubmed:28370240]

Biomed Chromatogr. 2017 Oct;31(10).

Pantoprazole, a proton pump inhibitor, is clinically used for the treatment of peptic diseases. An enantioselective LC-MS/MS method was developed and validated for the simultaneous determination of Pantoprazole enantiomers in human plasma. Pantoprazole enantiomers and the internal standard were extracted from plasma using acetonitrile. Chiral separation was carried on a Chiralpak IE column using the mobile phase consisted of 10 mm ammonium acetate solution containing 0.1% acetic acid-acetonitrile (28 : 72, v/v). MS analysis was performed on an API 4000 mass spectrometer. Multiple reactions monitoring transitions of m/z 384.1-->200.1 and 390.1-->206.0 were used to quantify Pantoprazole enantiomers and internal standard, respectively. For each enantiomer, no apparent matrix effect was found, the calibration curve was linear over 5.00-10,000 ng/mL, the intra- and inter-day precisions were below 10.0%, and the accuracy was within the range of -5.6% to 0.6%. This method was applied to the stereoselective pharmacokinetic studies in human after intravenous administration of S-(-)-Pantoprazole sodium injections. No chiral inversion was observed during sample storage, preparation procedure and analysis. While R-(+)-Pantoprazole was detected in human plasma with a slightly high concentration, which implied that S-(-)-Pantoprazole may convert to R-(+)-Pantoprazole in some subjects.

Up-regulation of autophagy is a mechanism of resistance to chemotherapy and can be inhibited by pantoprazole to increase drug sensitivity.[Pubmed:28378028]

Cancer Chemother Pharmacol. 2017 May;79(5):959-969.

BACKGROUND: Autophagy is a survival mechanism that allows recycling of cellular breakdown products, particularly in stressed cells. Here we evaluate the hypotheses that up-regulation of autophagy is a common mechanism of resistance to chemotherapy, and that drug resistance can be reversed by inhibiting autophagy with a proton pump inhibitor. METHODS: We exposed human PC3, LNCaP and MCF7 cells to seven clinically-used chemotherapy drugs +/- Pantoprazole, examined the up-regulation of autophagy and the effect on cellular proliferation by Western Blots, MTS assay and colony-forming assay. The distribution of drug effects and of autophagy was quantified in LNCaP tumor sections in relation to blood vessels and hypoxia by immunohistochemistry using gammaH2AX, cleaved caspase-3 and p62. RESULTS: All anticancer drugs led to up-regulation of autophagy in cultured tumor cells. Pantoprazole inhibited the induction of autophagy in a time- and dose-dependent manner, and sensitized cancer cells to the seven anti-cancer drugs. Treatment of LNCaP xenografts with paclitaxel induced both DNA damage and autophagy; autophagy was inhibited and markers of toxicity were increased by Pantoprazole. CONCLUSIONS: Induction of autophagy is a general mechanism associated with resistance to anticancer drugs and that its inhibition is a promising therapeutic strategy to enhance the effects of chemotherapy and improve clinical outcomes.

Pantoprazole (BY1023; SKF96022) is a proton pump inhibitor drug used for short-term treatment of erosion and ulceration of the esophagus caused by gastroesophageal reflux disease.

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