Mebendazole

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Mebendazole
Mebendazol.svg
Mebendazole3DanJ.gif
Systematic (IUPAC) name
methyl (5-benzoyl-1H-benzimidazol-2-yl)carbamate
Clinical data
Trade names Generic (formerly Vermox)
AHFS/Drugs.com monograph
MedlinePlus a682315
Pregnancy cat.
Legal status
Routes Oral
Pharmacokinetic data
Bioavailability 2-10%
Protein binding 95%
Metabolism Hepatic (extensive)
Half-life 3-6 hours
Excretion Faeces, urine (5-10%)
Identifiers
CAS number 31431-39-7 YesY
ATC code P02CA01 QP52AC09
PubChem CID 4030
DrugBank DB00643
ChemSpider 3890 YesY
UNII 81G6I5V05I YesY
KEGG D00368 YesY
ChEBI CHEBI:6704 YesY
ChEMBL CHEMBL685 YesY
Chemical data
Formula C16H13N3O3 
Mol. mass 295.293 g/mol
Physical data
Melt. point 288.5 °C (551 °F)
 YesY (what is this?)  (verify)

Mebendazole or MBZ a medicine used to treat infections by worms. This includes pinworms, roundworms, tapeworms, hookworms, and whipworms. It is taken by mouth and acts to paralyze and kill worms infecting the digestive tract. This reduces the parasite burden to a low level, and since these worms are unable to complete their reproductive cycle within a single human host, the parasite burden remains low unless the person is reinfected.[1] Mebendazole's low toxicity arises in part because very little of this drug is absorbed into the bloodstream. It is in the benzimidazole drug class.

It was introduced by Janssen Pharmaceutica in the early 1970s as an analog of an earlier drug, thiabendazole, relative to which it has the advantage of significantly reduced toxicity.[2][3] It is included in the World Health Organization's List of Essential Medicines, a list of the most important medication needed in a basic health system.[4]

Medical use[edit]

Mebendazole is a highly effective, broad-spectrum antihelmintic indicated for the treatment of nematode infestations, including roundworm, hookworm, whipworm, threadworm, pinworm, and the intestinal form of trichinosis prior to its spread into the tissues beyond the digestive tract. Other drugs are used to treat worm infections outside the digestive tract, as mebendazole is poorly absorbed into the bloodstream.[3] Mebendazole is used alone in those with mild to moderate infestation. Mebendazole kills parasites relatively slowly, and in those with very heavy infestations it can cause some parasites to migrate out of the digestive system, leading to appendicitis, bile duct problems, or intestinal perforation. To avoid this, heavily infested patients may be treated with piperazine, either before or instead of mebendazole. Piperazine paralyses the parasites causing them to pass in the feces.[5]

Mebendazole and other benzimidazole antithelmetics are active against both larval and adult stages of nematodes and in the cases of roundworm and whipworm, kill the eggs as well. Paralysis and death of the parasites occurs slowly, and elimination in the feces may require several days.[3]

Special Populations[edit]

Mebendazole is Pregnancy Category C, which means that it has been shown to cause ill effects in pregnancy in animal models and there are no adequate studies of its effects in human pregnancy. It is unknown whether it can be passed by breast feeding.[1]

Adverse effects[edit]

Mebendazole sometimes causes diarrhea, abdominal pain, and elevated liver enzymes. In rare cases it has been associated with a dangerously low white blood cell count, low platelet count, and hair loss,[1][6] with a risk of agranulocytosis in rare cases

Drug interactions[edit]

Carbamazepine and phenytoin lower serum levels of mebendazole. Cimetidine does not appreciably raise serum mebendazole (in contrast to the similar drug albendazole), consistent with its poor systemic absorption.[7][8]

Stevens–Johnson syndrome and the more severe toxic epidermal necrolysis can occur when mebendazole is combined with high doses of metronidazole.[9]

Mechanism[edit]

Mebendazole is thought to work by selectively inhibiting the synthesis of microtubules in parasitic worms, and by destroying extant cytoplasmic microtubes in their intestinal cells, thereby blocking the uptake of glucose and other nutrients, resulting in the gradual immobilization and eventual death of the helminths.[3]

Discontinuation in United States[edit]

The last manufacturer of mebendazole in the United States, Teva Pharmaceuticals, announced on October 7, 2011, they have ceased manufacture of this product. As of December, 2011, it is no longer available from any manufacturer in the USA. No reason was given publicly for this discontinuation.[10] Mebendazole formulations can be made by a compounding pharmacy at the request of a doctor. Mebendazole is still distributed in international markets by Johnson and Johnson and a number of generic manufacturers.[11]

Research[edit]

Several studies show mebendazole exhibits potent antitumor properties. MBZ significantly inhibited cancer cell growth, migration and metastatic formation of adrenocortical carcinoma, both in vitro and in vivo.[12] Treatment of lung cancer cell lines with MBZ caused mitotic arrest, followed by apoptotic cell death with the feature of caspase activation and cytochrome c release.[13] MBZ induced a dose- and time-dependent apoptotic response in human lung cancer cell lines,[14] and apoptosis via Bcl-2 inactivation in chemoresistant melanoma cells.[15]

References[edit]

  1. ^ a b c Finberg R, Fingeroth J in Longo DL, Fauci AS, Kasper DL, Hauser SL, Jameson JL, Loscalzo, Ed. Harrison's Principles of Internal Medicine, 18th ed., McGraw-Hill, 2012, Chapter 217.
  2. ^ Chavarría AP, Swartzwelder JC, Villarejos VM, Zeledón R (September 1973). "Mebendazole, an effective broad-spectrum anthelmintic". Am. J. Trop. Med. Hyg. 22 (5): 592–5. PMID 4729739. 
  3. ^ a b c d Petri WA in Brunton LL, Chabner BA, Knollmann BC, Ed. Goodman and Gilman's The Pharmacological Basis of Therapeutics, 12th ed., Chapter 42. McGraw-Hill, 2011 New York.
  4. ^ "WHO Model List of EssentialMedicines". World Health. 
  5. ^ Martin AR in Wilson and Gisvold's Textbook of Organic Medicinal and Pharmaceutical Chemistry, 8th edition, Doerge RF, ed. J.B. Lippincott, 1982, Chapter 4
  6. ^ Andersohn F, Konzen C, Garbe E (May 2007). "Systematic review: agranulocytosis induced by nonchemotherapy drugs". Ann. Intern. Med. 146 (9): 657–65. doi:10.7326/0003-4819-146-9-200705010-00009. PMID 17470834. 
  7. ^ "Drug Interactions". Medicine chest. Retrieved 2008-05-06. 
  8. ^ Luder PJ, Siffert B, Witassek F, Meister F, Bircher J; Siffert; Witassek; Meister; Bircher (1986). "Treatment of hydatid disease with high oral doses of mebendazole. Long-term follow-up of plasma mebendazole levels and drug interactions". European journal of clinical pharmacology 31 (4): 443–448. doi:10.1007/bf00613522. PMID 3816925.  edit
  9. ^ Chen, K. T.; Twu, S. J.; Chang, H. J.; Lin, R. S. (2003). "Outbreak of Stevens-Johnson Syndrome / Toxic Epidermal Necrolysis Associated with Mebendazole and Metronidazole Use Among Filipino Laborers in Taiwan". American Journal of Public Health 93 (3): 489–492. doi:10.2105/ajph.93.3.489. PMC 1447769. PMID 12604501.  edit
  10. ^ "Drug Shortages Bulletin 750". American Society of Health-System Pharmacists. Retrieved 2011-12-18. 
  11. ^ http://zenrx.org/, retrieved 2014-06-12  Missing or empty |title= (help)
  12. ^ Martarelli D, Pompei P, Baldi C, Mazzoni G (April 2008). "Mebendazole inhibits growth of human adrenocortical carcinoma cell lines implanted in nude mice". Cancer Chemother. Pharmacol. 61 (5): 809–17. doi:10.1007/s00280-007-0538-0. PMID 17581752. 
  13. ^ Sasaki J, Ramesh R, Chada S, Gomyo Y, Roth JA, Mukhopadhyay T (November 2002). "The anthelmintic drug mebendazole induces mitotic arrest and apoptosis by depolymerizing tubulin in non-small cell lung cancer cells". Mol. Cancer Ther. 1 (13): 1201–9. PMID 12479701. 
  14. ^ Mukhopadhyay T, Sasaki J, Ramesh R, Roth JA (September 2002). "Mebendazole elicits a potent antitumor effect on human cancer cell lines both in vitro and in vivo". Clin. Cancer Res. 8 (9): 2963–9. PMID 12231542. 
  15. ^ Doudican N, Rodriguez A, Osman I, Orlow SJ (August 2008). "Mebendazole induces apoptosis via Bcl-2 inactivation in chemoresistant melanoma cells". Mol. Cancer Res. 6 (8): 1308–15. doi:10.1158/1541-7786.MCR-07-2159. PMID 18667591.