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. B3 (AU) B (US)
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 (sold under various brand names including Somac, Tecta, Pantoloc, Dew-Pantadom, Controloc,Panprax, Pansiv, Protium,Prazolin, Protonix, Pantecta, Pantoheal, Pantpas, Ppi-40, and Neoppi) is a proton pump inhibitor drug that inhibits gastric acid secretion.

Use[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.[citation needed] It can be used as a maintenance therapy for long term use after initial response is obtained.

This medication may affect the results of certain lab tests, such as drug screenings (pantoprazole can cause a false positive for THC, the psychoactive component of cannabis[1][2]). It has also been known to cause false positive for benzodiazepines.[citation needed]

Adverse effects[edit]

Antacid preparations such as pantoprazole work by suppressing the acid-mediated breakdown of proteins. This leads to an elevated risk of developing food and drug allergies due to undigested proteins passing into the gastrointestinal tract where sensitisation occurs. It is unclear whether this risk occurs with short-term or only long-term use.[3]

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, 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.[4]
  • Cardiovascular: Increase in a chemical that suppresses the production of nitric oxide by 25% in humans, which have 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 period of time.[5]

Pharmacology[edit]

Wyeth pantoprazole 20mg.

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 acidic pH of stomach, thus it is usually given with a pro kinetic 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), approximately 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 to 2.5 h
  • Tmax, Oral, delayed-release tablets: 2.5 h
  • Tmax, Oral, delayed-release tablets: 1.5 to 2 hours (pediatrics)

Distribution

  • Protein binding: about 98% to primarily albumin
  • Vd, extensive metabolizers (IV): approximately 11 L 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), approximately 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 5.34 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) and is currently marketed under the brand name Protonix by Wyeth-Ayerst Laboratories, Pansiv by Saharsh Biologicals, Pantec by Concept Pharmaceuticals, Somac by Pfizer, API by Vanguard Therapeutics, Astropan by Astron Lifesciences, Fenix by Bosnalijek, Pantecta by Novartis, Pantoloc, Controloc or Somac by Nycomed, Tecta by Nycomed in Canada, Protium in the UK, Inipomp by Sanofi or Eupantol by Nycomed in France, Pantozol by Nycomed in Germany, Pantodac, Perizole by Obsurge Biotech and Pansped in India, Zurcazol in Greece, Protonex by Abdi İbrahim in Turkey, Pantup in Ireland, Pantomed in Belgium, TopZole in South Africa, Nolpaza and Controloc in Romania and as UXL-D in India, Pantid by Opsonin in Bangladesh. Pantid is the first brand in the world which is providing in double Alu-Alu sachet packaging to prevent its degradation from moisture & light.The generic pantoprazole sodium is available in the U.S. from Kremers Urban, Teva, and Torrent Pharma. It is available by prescription in delayed-release tablets. It is also available for intravenous use.

On 24 December 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] The combination of domperidone 10 mg and pantoprazole 40 mg is available in India under the brand name Pantazone, Pantop-D, Rantop-D. Also, Indian pharmaceutical company Sun Pharmaceutical produces pantoprazole under the brand name Pantasan, which is available in Russia and Belarus. In Bangladesh Apex Pharma Limited markets pantoprazole under the brand name Pantrol. It is also available under the brand name Prazolin marketed by Rephco Pharmaceuticals Limited. It is also marketed by Chemist Laboratories Ltd. under the brand name Pantochem.

References[edit]

  1. ^ Protonix package insert 12/07
  2. ^ "What causes false positives in marijuana drug testing?". LiveStrong. 
  3. ^ Pali-Schöll I, Jensen-Jarolim E (April 2011). "Anti-acid medication as a risk factor for food allergy". Allergy 66 (4): 469–77. doi:10.1111/j.1398-9995.2010.02511.x. PMID 21121928. 
  4. ^ [Dr. John Cooke, chair of Methodist Hospital's cardiovascular services] [Houston Chronicle Health Zone dated Thursday, July 11, 2013 chron.com/refluxmeds] (Journal: Circulation)
  5. ^ [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]