Praziquantel Explained

Watchedfields:changed
Verifiedrevid:464213440
Iupac Name:(RS)-2-(Cyclohexylcarbonyl)-1,2,3,6,7,11b-hexahydro-4H-pyrazino[2,1-''a'']isoquinolin-4-one
Width:215
Tradename:Biltricide
Dailymedid:Praziquantel
Pregnancy Au:B1
Legal Ca:Rx-only
Legal Ca Comment:[1]
Legal Us:Rx-only
Legal Us Comment:(human use),
OTC (veterinary use)[2]
Routes Of Administration:Human use: by mouth (tablets)
Bioavailability:Relatively small
Metabolism:Liver
Elimination Half-Life:0.8–1.5 hours (main metabolites: 4–5 hours)
Excretion:Kidney (mainly)
Cas Number:55268-74-1
Atc Prefix:P02
Atc Suffix:BA01
Pubchem:4891
Drugbank:DB01058
Chemspiderid:4722
Unii:6490C9U457
Kegg:D00471
Chembl:976
C:19
H:24
N:2
O:2
Smiles:O=C4N2C(c1c(cccc1)CC2)CN(C(=O)C3CCCCC3)C4
Stdinchi:1S/C19H24N2O2/c22-18-13-20(19(23)15-7-2-1-3-8-15)12-17-16-9-5-4-6-14(16)10-11-21(17)18/h4-6,9,15,17H,1-3,7-8,10-13H2
Stdinchikey:FSVJFNAIGNNGKK-UHFFFAOYSA-N
Melting Point:136
Melting High:138

Praziquantel (PZQ), sold under the brandname Biltricide among others, is a medication used to treat a number of types of parasitic worm infections in mammals, birds, amphibians, reptiles, and fish. In humans specifically, it is used to treat schistosomiasis, clonorchiasis, opisthorchiasis, tapeworm infections, cysticercosis, echinococcosis, paragonimiasis, fasciolopsiasis, and fasciolosis. It should not be used for worm infections of the eye.[3] It is taken by mouth.[4]

Side effects in humans may include poor coordination, abdominal pain, vomiting, headache, and allergic reactions.[3] While it may be used during pregnancy, it is not recommended for use during breastfeeding.[3] Praziquantel is in the anthelmintic class of medications.[4] It works partly by affecting the function of the worm's sucker.[4]

Praziquantel was approved for medical use in the United States in 1982.[4] It is on the World Health Organization's List of Essential Medicines.[5]

Medical uses

Praziquantel is used to treat diseases caused by infection with several types of internal/gastrointestinal, and external parasites, including:

Side effects

The majority of side effects develop due to the release of the contents of the parasites as they are killed and the consequent host immune reaction. The heavier the parasite burden, the heavier and more frequent the side effects normally are.

Pregnancy

The WHO states praziquantel is safe during pregnancy.[21] Animal studies have failed to reveal evidence of fetal harm. Praziquantel is effective in reducing schistosomiasis during pregnancy.[22] Another trial found that treatment with praziquantel did not increase the rates of low birthweight, fetal death, or congenital anomalies.[23]

Drug interactions

The antibiotic rifampicin decreases plasma concentrations of praziquantel.[24]

Carbamazepine and phenytoin are reported to reduce the bioavailability of praziquantel.[25] Chloroquine also reduces its bioavailability.[26]

The drug cimetidine heightens praziquantel bioavailability.[27] [28]

Mechanism of action

The drug's mode of action is not exactly known at present, but experimental evidence indicates praziquantel increases the permeability of the membranes of schistosome cells towards calcium ions. The drug thereby induces contraction of the parasites' muscle, resulting in paralysis in the contracted state. The dying parasites are dislodged from their site of action in the host organism and may enter systemic circulation or may be destroyed by host immune reaction (phagocytosis). Additional mechanisms including focal disintegrations and disturbances of oviposition (laying of eggs) are seen in other types of sensitive parasites.

Another hypothesis regarding the mechanism of action is that it interferes with adenosine uptake in worms.[29] This effect may have therapeutical relevance given that the schistosome, as the Taenia and the Echinococcus (other praziquantel-sensitive parasites), is unable to synthesize purines, such as adenosine, de novo.

Bayer's Animal Health Division website states, "Praziquantel is active against cestodes (tapeworms). Praziquantel is absorbed, metabolized in the liver, and excreted in the bile. Upon entering the digestive tract from the bile, cestocidal activity is exhibited. Following exposure to praziquantel, the tapeworm loses its ability to resist digestion by the mammalian host. Because of this, whole tapeworms, including the scolices (plural of "scolex"), are very rarely passed after administration of praziquantel. In many instances, only disintegrated and partially digested pieces of tapeworms will be seen in the stool. The majority of tapeworms are digested and are not found in the feces."[30]

Praziquantel is administered as a racemate, but only the (R)-enantiomer is biologically active; the enantiomers may be separated using a resolution of an amine obtained from praziquantel.[31]

Pharmacokinetics

Praziquantel is well absorbed (about 80%) from the gastrointestinal tract. However, due to extensive first-pass metabolism, only a relatively small amount enters systemic circulation. Praziquantel has a serum half-life of 0.8 to 1.5 hours in adults with normal renal and liver function. Metabolites have a half-life of 4 to 5 hours. In patients with significantly impaired liver function (Child-Pugh score B and C), the serum half-life is increased to 3 to 8 hours. Praziquantel and its metabolites are mainly excreted renally; within 24 h after a single oral dose, 70 to 80% is found in urine, but less than 0.1% as the unchanged drug. Praziquantel is metabolized through the cytochrome P450 pathway via CYP3A4. Agents that induce or inhibit CYP3A4 such as phenytoin, rifampin, and azole antifungals will affect the metabolism of praziquantel.

Praziquantel has a particularly dramatic effect on patients with schistosomiasis. Studies of those treated have shown that within six months of receiving a dose of praziquantel, up to 90% of the damage done to internal organs due to schistosomiasis infection can be reversed.[13]

History

Praziquantel was developed in the laboratories for parasitological research of Bayer AG and Merck KGaA in Germany (Elberfeld and Darmstadt) in the mid-1970s.

Society and culture

Brand names

Regulatory approval

Praziquantel is on the World Health Organization's List of Essential Medicines.

Praziquantel is not licensed for use in humans in the UK, but it can be imported when necessary on a named-patient basis.[33] It is available in the UK as a veterinary anthelmintic.

Praziquantel is FDA approved in the US for the treatment of schistosomiasis and liver flukes, although it is effective in other infections.[34]

Veterinary medicine

It may cause problems in dogs with MDR1 mutations.[36]

See also

External links

Notes and References

  1. Web site: Product monograph brand safety updates . Health Canada . February 2024 . 24 March 2024.
  2. Web site: Farnam Pet Press Release. TRUSTED D-WORM offers product for tapeworm management. Farnam Companies, Inc.. 3 October 2016. dead. https://web.archive.org/web/20081014085523/http://www.farnampet.com/press_releases.php?id=100674. 14 October 2008.
  3. Book: WHO Model Formulary 2008 . 2009 . 9789241547659 . ((World Health Organization)) . Stuart MC, Kouimtzi M, Hill SR . 10665/44053 . World Health Organization . World Health Organization . free . 88, 593 .
  4. Web site: Praziquantel. The American Society of Health-System Pharmacists. 8 December 2016. live. https://web.archive.org/web/20161220223422/https://www.drugs.com/monograph/praziquantel.html. 20 December 2016.
  5. Book: ((World Health Organization)) . World Health Organization model list of essential medicines: 21st list 2019 . 2019 . 10665/325771 . World Health Organization . World Health Organization . Geneva . WHO/MVP/EMP/IAU/2019.06. License: CC BY-NC-SA 3.0 IGO . free .
  6. Matthaiou DK, Panos G, Adamidi ES, Falagas ME . Albendazole versus praziquantel in the treatment of neurocysticercosis: a meta-analysis of comparative trials . PLOS Neglected Tropical Diseases . 2 . 3 . e194 . March 2008 . 18335068 . 2265431 . 10.1371/journal.pntd.0000194 . Carabin H . free .
  7. Web site: CDC - Taeniasis - Resources for Health Professionals. CDC. 2020-05-20. 2024-05-02.
  8. Web site: CDC - Diphyllobothrium - Resources for Health Professionals. CDC. 2020-05-20. 2024-05-02.
  9. Web site: CDC - Hymenolepis - Resources for Health Professionals. CDC. 2020-05-20. 2024-05-02.
  10. Web site: CDC - DPDx - Bertiella infection - Treatment Information. CDC. 2013-11-29. 2024-05-02.
  11. Book: Feline clinical parasitology. Bowman DD, Hendrix CM, Lindsay DS, Barr SC . First. 2002. 275. Iowa State University. Ames, Iowa. 0-8138-0333-0. live. https://web.archive.org/web/20170910151740/https://books.google.com/books?id=mvpsA9dGdpAC&pg=PA278&dq=%22toxocara+cati%22&hl=en&sa=X&ei=s-JpT7GjFYKviALbkrnNBQ&ved=0CD0Q6AEwAQ#v=onepage&q=%22toxocara%20cati%22&f=false. 2017-09-10.
  12. Tchuenté LA, Shaw DJ, Polla L, Cioli D, Vercruysse J . Efficacy of praziquantel against Schistosoma haematobium infection in children . The American Journal of Tropical Medicine and Hygiene . 71 . 6 . 778–782 . December 2004 . 15642971 . 10.4269/ajtmh.2004.71.778 . free .
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  14. Shen C, Kim J, Lee JK, Bae YM, Choi MH, Oh JK, Lim MK, Shin HR, Hong ST . Collection of Clonorchis sinensis adult worms from infected humans after praziquantel treatment . The Korean Journal of Parasitology . 45 . 2 . 149–152 . June 2007 . 17570980 . 2526309 . 10.3347/kjp.2007.45.2.149 . dead . https://archive.today/20121220070503/http://www.parasitol.or.kr/kjp/abstracts/2007_149.html . 2012-12-20 .
  15. Web site: Opisthorchiasis - Treatment Information. CDC - DPDx. 2013-11-29. 2015-09-07.
  16. Web site: CDC - Paragonimiasis - General Information - Frequently Asked Questions (FAQs). 2019-04-19. www.cdc.gov. en-us. 2019-10-02.
  17. Web site: CDC - Paragonimiasis - Resources for Health Professionals. 2019-05-24. www.cdc.gov. en-us. 2019-10-02.
  18. Mas-Coma S, Bargues MD, Valero MA . Fascioliasis and other plant-borne trematode zoonoses . International Journal for Parasitology . 35 . 11–12 . 1255–1278 . October 2005 . 16150452 . 10.1016/j.ijpara.2005.07.010 .
  19. Rim HJ, Chu DS, Lee JS, Joo KH, Won CY . [Anthelmintic Effects Of Various Drugs Against Metagonimiasis] . Kisaengch'unghak Chapchi. The Korean Journal of Parasitology . 16 . 2 . 117–122 . December 1978 . 12902772 . 10.3347/kjp.1978.16.2.117 .
  20. Taraschewski H, Mehlhorn H, Bunnag D, Andrews P, Thomas H . Effects of praziquantel on human intestinal flukes (Fasciolopsis buski and Heterophyes heterophyes) . Zentralblatt Fur Bakteriologie, Mikrobiologie, und Hygiene. Series A, Medical Microbiology, Infectious Diseases, Virology, Parasitology . 262 . 4 . 542–550 . November 1986 . 3799097 . 10.1016/s0176-6724(86)80148-1 .
  21. Web site: WHO | Strategy . https://web.archive.org/web/20070617184031/http://www.who.int/schistosomiasis/strategy/en/ . dead . June 17, 2007 . World Health Organisation: Schistosomiasis . 4 March 2020.
  22. Tweyongyere R, Mawa PA, Emojong NO, Mpairwe H, Jones FM, Duong T, Dunne DW, Vennervald BJ, Katunguka-Rwakishaya E, Elliott AM . Effect of praziquantel treatment of Schistosoma mansoni during pregnancy on intensity of infection and antibody responses to schistosome antigens: results of a randomised, placebo-controlled trial . BMC Infectious Diseases . 9 . 32 . 32 . March 2009 . 19296834 . 2666740 . 10.1186/1471-2334-9-32 . free .
  23. Olveda RM, Acosta LP, Tallo V, Baltazar PI, Lesiguez JL, Estanislao GG, Ayaso EB, Monterde DB, Ida A, Watson N, McDonald EA, Wu HW, Kurtis JD, Friedman JF . Efficacy and safety of praziquantel for the treatment of human schistosomiasis during pregnancy: a phase 2, randomised, double-blind, placebo-controlled trial . The Lancet. Infectious Diseases . 16 . 2 . 199–208 . February 2016 . 26511959 . 4752899 . 10.1016/S1473-3099(15)00345-X .
  24. Ridtitid W, Wongnawa M, Mahatthanatrakul W, Punyo J, Sunbhanich M . Rifampin markedly decreases plasma concentrations of praziquantel in healthy volunteers . Clinical Pharmacology and Therapeutics . 72 . 5 . 505–513 . November 2002 . 12426514 . 10.1067/mcp.2002.129319 . 30853881 .
  25. Quinn DI, Day RO . Drug interactions of clinical importance. An updated guide . Drug Safety . 12 . 6 . 393–452 . June 1995 . 8527014 . 10.2165/00002018-199512060-00005 . 34890344 .
  26. Masimirembwa CM, Naik YS, Hasler JA . The effect of chloroquine on the pharmacokinetics and metabolism of praziquantel in rats and in humans . Biopharmaceutics & Drug Disposition . 15 . 1 . 33–43 . January 1994 . 8161714 . 10.1002/bdd.2510150103 . 45098166 .
  27. Metwally A, Bennett JL, Botros S, Ebeid F . Effect of cimetidine, bicarbonate and glucose on the bioavailability of different formulations of praziquantel . Arzneimittel-Forschung . 45 . 4 . 516–518 . April 1995 . 7779153 .
  28. Jung H, Medina R, Castro N, Corona T, Sotelo J . Pharmacokinetic study of praziquantel administered alone and in combination with cimetidine in a single-day therapeutic regimen . Antimicrobial Agents and Chemotherapy . 41 . 6 . 1256–1259 . June 1997 . 9174180 . 163896 . 10.1128/AAC.41.6.1256 .
  29. Angelucci F, Basso A, Bellelli A, Brunori M, Pica Mattoccia L, Valle C . The anti-schistosomal drug praziquantel is an adenosine antagonist . Parasitology . 134 . Pt 9 . 1215–1221 . August 2007 . 17428352 . 10.1017/S0031182007002600 . 22482704 .
  30. Web site: Archived copy . 2010-03-24 . 2007-05-18 . https://web.archive.org/web/20070518114008/http://bayer.naccvp.com/view_label.php . dead .
  31. Woelfle M, Seerden JP, de Gooijer J, Pouwer K, Olliaro P, Todd MH . Resolution of praziquantel . PLOS Neglected Tropical Diseases . 5 . 9 . e1260 . September 2011 . 21949890 . 3176743 . 10.1371/journal.pntd.0001260 . Geary TG . free .
  32. Web site: BILTRICIDE- praziquantel tablet, film coated (NDC Code(s): 50419-747-01). DailyMed. July 2015. 2015-09-08. live. https://web.archive.org/web/20150910035308/http://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=34ce1cdd-648e-4f1e-8512-bf3d4cc22eb9. 2015-09-10.
  33. Web site: Antihelmintics - Medicines for Worms; threadword, roundworm. Patient. 2015-06-15. live. https://web.archive.org/web/20150618002318/http://patient.info/health/antihelmintics-medicines-for-worms. 2015-06-18.
  34. Book: 12. McGraw-Hill Education / Medical. 9780071624428. Brunton L, Chabner B, Knollman B . Goodman and Gilman's The Pharmacological Basis of Therapeutics, Twelfth Edition. New York. 2011-01-10.
  35. Schmahl G, Taraschewski H . Treatment of fish parasites. 2. Effects of praziquantel, niclosamide, levamisole-HCl, and metrifonate on monogenea (Gyrodactylus aculeati, Diplozoon paradoxum) . Parasitology Research . 73 . 4 . 341–351 . 1987 . 3615395 . 10.1007/bf00531089 . 12241452 .
  36. Web site: List of Drugs That Cause Sensitivity to Dogs With mdr1 Mutation . 2016-06-05 . live . https://web.archive.org/web/20160705112241/http://www.collieassociation.co.uk/health/MDR1leaflet.pdf . 2016-07-05 . www.collieassociation.co.uk .

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