Pantoprazole

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Pantoprazole
Pantoprazole.svg
Systematic (IUPAC) name
(RS)-6-(Difluoromethoxy)-2-[(3,4-dimethoxypyridin-2-yl)methylsulfinyl]-1H-benzo[d]imidazole
Clinical data
Trade names Protonix
AHFS/Drugs.com monograph
MedlinePlus a601246
Licence data US FDA:link
Pregnancy cat.
Legal status
  • Prescription only
Routes Oral and intravenous
Pharmacokinetic data
Bioavailability 77%
Metabolism Hepatic (CYP3A4)
Half-life 1 hour
Excretion Renal
Identifiers
CAS number 102625-70-7 YesY
ATC code A02BC02
PubChem CID 4679
DrugBank DB00213
ChemSpider 4517 YesY
UNII D8TST4O562 YesY
KEGG D05353 YesY
ChEBI CHEBI:7915 YesY
ChEMBL CHEMBL1502 YesY
Chemical data
Formula C16H15F2N3O4S 
Mol. mass 383.371 g/mol
 YesY (what is this?)  (verify)

Pantoprazole is a proton pump inhibitor drug that inhibits gastric acid secretion. It was first marketed under the brand name Protonix.

Medical uses[edit]

Pantoprazole is used for short-term treatment of erosion and ulceration of the oesophagus caused by gastroesophageal reflux disease. Initial treatment is generally of eight weeks' duration, after which another eight-week course of treatment may be considered if necessary.[1] It can be used as a maintenance therapy for long-term use after initial response is obtained. Pantoprazole may also be used in combination with antibiotics to treat ulcers caused by Helicobacter pylori.[2] When treating H. pylori ulcers, pantoprazole is given twice daily,[3] in contrast to gastroesophageal reflux disease, where it is usually given once daily.[1] Typical treatment courses for H. pylori range from 10 to 14 days.[3]

Adverse effects[edit]

  • Infection: Stomach acid plays a role in killing ingested bacteria. Use of pantoprazole may increase the chance of developing infections such as pneumonia, particularly in hospitalized patients.[4]

Common[edit]

  • Gastrointestinal: abdominal pain (3%), diarrhea (4%), flatulence (4%)
  • Neurologic: headache (5%)

Serious[edit]

  • Gastrointestinal: atrophic gastritis, Clostridium difficile diarrhea
  • Hematologic: thrombocytopenia (less than 1%)
  • Immunologic: Stevens-Johnson syndrome, toxic epidermal necrolysis
  • Musculoskeletal: Muscle disorders, bone fracture and infection, Clostridium difficile infection, osteoporosis-related hip fracture, rhabdomyolysis
  • Renal: interstitial nephritis (rare)
  • Nutrition: may reduce the absorption of important nutrients, vitamins and minerals, as well as medications, leaving users at increased risk for pneumonia[5]
  • Cardiovascular: increase in a chemical that suppresses the production of nitric oxide by 25% in humans, which has proven to relax and protect arteries and veins, causes blood vessels to constrict, a development that could lead to a number of cardiovascular problems if continued for a prolonged time[5]

Pharmacology[edit]

Wyeth pantoprazole 20-mg

Pantoprazole is metabolized in the liver by the cytochrome P450 system.[6] Metabolism mainly consists of demethylation by CYP2C19 followed by sulfation. Another metabolic pathway is oxidation by CYP3A4. Pantoprazole metabolites are not thought to have any pharmacological significance. Pantoprazole is relatively free of drug interactions;[7] however, it may alter the absorption of other medications that depend on the amount of acid in the stomach, such as ketoconazole or digoxin. Generally inactive at the acidic pH of stomach, thus it is usually given with a prokinetic drug. Pantoprazole binds irreversibly to H+K+ATPase (proton pumps) and suppresses the secretion of acid. As it binds irreversibly to the pumps, new pumps have to be made before acid production can be resumed. The drug's plasma half-life is about 2 hours.[8]

Pharmacokinetics[edit]

Absorption

  • Bioavailability: (oral, delayed release tablets), about 77%
  • Effect of food: (oral, delayed-release tablets), AUC and Cmax no effect, Tmax variable, absorption delayed, no net effect
  • Effect of food: (oral, for-delayed-release suspension), administer 30 minutes before a meal
  • Tmax, oral, delayed-release suspension: 2.0 to 2.5 h
  • Tmax, oral, delayed-release tablets: 2.5 h
  • Tmax, oral,delayed-release tablets: 1.5 to 2.0 hours (pediatrics)

Distribution

  • Protein binding: about 98% to primarily albumin
  • Vd, extensive metabolizers (IV): about 11 to 23.6 l
  • Vd, pediatrics (oral): 0.21 to 0.43 l/kg.

Metabolism

  • Hepatic; cytochrome P450 CYP2C19; minor metabolism from CYP3A4, 2D6, and 2C9

Excretion

  • Fecal: (oral or IV, normal metabolizers), 18%
  • Renal: (oral or IV, normal metabolizers), about 71%, none as unchanged
  • Dialyzable: no (hemodialysis)
  • Total body clearance: (IV) 7.6 to 14 l/hour.
  • Total body clearance: (oral, pediatrics) 0.18 to 2.08 l/h/kg

Elimination half-life

  • Oral or IV, 1 hour
  • Oral or IV, slow metabolizers, 3.5 to 10 hours
  • Pediatrics, 0.7 to 5.3 hours

Availability[edit]

Pantoprazole was developed by Altana (owned by Nycomed) and was licensed in the USA to Wyeth (which was taken over by Pfizer). It was initially marketed under the brand name Protonix by Wyeth-Ayerst Laboratories, and now is available as a generic. It is available by prescription in delayed-release tablets. It is also available for intravenous use.

On December 24, 2007, Teva Pharmaceutical released an AB-rated generic alternative to Protonix.[9] This was followed by generic equivalents from Sun Pharma and Kudco Pharma. Wyeth sued all three for patent infringement and launched its own generic version of Protonix with Nycomed.[10][11]

On October 18, 2010, the U.S. Food and Drug Administration (FDA) accepted the filing of an ANDA for a delayed-release generic version of Protonix by Canadian company IntelliPharmaCeutics.[12]

Brand names[edit]

Pantoprazole is available from a range of international suppliers under brand names including Pantazone, Pantop-D, Pantasan, Pantrol, Prazolin, Pantochem, Pansev, Pantec, Somac, API, Tecta, Protium, Pantodac, Perizole, Pansped, Percazole, Astropan, Fenix, Pantecta, Pantoloc, Controloc, Somac, Tecta, Protium, Inipomp, Eupantol, Pantozol, Pantodac, Perizole, Pansped, Zurcazol, Protonex, Pantup, Pantomed, TopZole, Nolpaza, Controloc, UXL-D, Pantid, Pantogen, Pantpas, Proton, and Prazolin.

See also[edit]

References[edit]

  1. ^ a b Katz, Philip O; Gerson, Lauren B; Vela, Marcelo F (19 February 2013). "Guidelines for the Diagnosis and Management of Gastroesophageal Reflux Disease". The American Journal of Gastroenterology 108 (3): 308–328. doi:10.1038/ajg.2012.444. 
  2. ^ Dammann, HG; Fölsch, UR; Hahn, EG; von Kleist, DH; Klör, HU; Kirchner, T; Strobel, S; Kist, M (March 2000). "Eradication of H. pylori with pantoprazole, clarithromycin, and metronidazole in duodenal ulcer patients: a head-to-head comparison between two regimens of different duration.". Helicobacter 5 (1): 41–51. PMID 10672051. 
  3. ^ a b Chey, WD; Wong, BC; Practice Parameters Committee of the American College of, Gastroenterology (August 2007). "American College of Gastroenterology guideline on the management of Helicobacter pylori infection.". The American journal of gastroenterology 102 (8): 1808–25. PMID 17608775. 
  4. ^ Herzig, SJ; Doughty, C; Lahoti, S; Marchina, S; Sanan, N; Feng, W; Kumar, S (November 2014). "Acid-suppressive medication use in acute stroke and hospital-acquired pneumonia.". Annals of neurology 76 (5): 712–8. PMID 25164323. 
  5. ^ a b [Dr. John Cooke, chair of Methodist Hospital's cardiovascular services] [Houston Chronicle Health Zone dated Thursday, July 11, 2013 chron.com/refluxmeds] (Journal: Circulation)
  6. ^ Meyer, U A (1996). "Metabolic interactions of the proton-pump inhibitors lansoprazole, omeprazole and pantoprazole with other drugs". European journal of gastroenterology & hepatology 8 (Suppl 1): S21–25. doi:10.1097/00042737-199610001-00005. 
  7. ^ Steinijans, V. W.; Huber, R.; Hartmann, M.; Zech, K.; Bliesath, H.; Wurst, W.; Radtke, H. W. (1996). "Lack of pantoprazole drug interactions in man: An updated review". International Journal of Clinical Pharmacology and Therapeutics 34 (6): 243–262. PMID 8793611. 
  8. ^ Sachs G, Shin JM, Hunt R (December 2010). "Novel approaches to inhibition of gastric acid secretion". Curr Gastroenterol Rep 12 (6): 437–47. doi:10.1007/s11894-010-0149-5. PMC 2974194. PMID 20924727. 
  9. ^ Teva Announces Launch Of Generic Protonix Tablets
  10. ^ Rubenstein, Sarah (29 January 2008). "Wyeth Plans Generic Protonix; Litigation With Teva to Continue". The Wall Street Journal. p. D9. Retrieved 25 October 2009. 
  11. ^ "Nycomed and Wyeth announce launch of an own generic version of PROTONIX - lawsuit to defend patent continues". Retrieved 25 October 2009. [dead link]
  12. ^ IntelliPharmaCeutics Press Release

External links[edit]