Chemistry:Praziquantel

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Short description: Medication
Praziquantel
Praziquantel.svg
(R)-praziquantel-from-xtal-3D-bs-17.png
Clinical data
Pronunciation/ˌpræzɪˈkwɒntɛl/
Trade namesBiltricide
AHFS/Drugs.comMonograph
MedlinePlusa608048
License data
Pregnancy
category
  • AU: B1
  • US: B (No risk in non-human studies)
Routes of
administration		Human use: by mouth (tablets)
ATC code
Legal status
Legal status
Pharmacokinetic data
BioavailabilityRelatively small
MetabolismLiver
Elimination half-life0.8–1.5 hours (main metabolites: 4–5 hours)
ExcretionUrine (mainly)
Identifiers
CAS Number
PubChem CID
DrugBank
ChemSpider
UNII
KEGG
ChEMBL
Chemical and physical data
FormulaC19H24N2O2
Molar mass312.413 g·mol−1
3D model (JSmol)
Melting point136 to 138 °C (277 to 280 °F)
  (verify)

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.[2] In humans specifically, it is used to treat schistosomiasis, clonorchiasis, opisthorchiasis, tapeworm infections, cysticercosis, echinococcosis, paragonimiasis, fasciolopsiasis, and fasciolosis.[2] It should not be used for worm infections of the eye.[3] It is taken by mouth.[2]

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.[2] It works partly by affecting the function of the worm's sucker.[2]

Praziquantel was approved for medical use in the United States in 1982.[2] It is on the World Health Organization's List of Essential Medicines.[4]

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.[citation needed]

  • Central nervous system (CNS): Frequently occurring side effects are dizziness, headache, and malaise. Drowsiness, somnolence, fatigue, and vertigo have also been seen. Almost all patients with cerebral cysticercosis experience CNS side effects related to the cell-death of the parasites (headache, worsening of pre-existing neurological problems, seizures, arachnoiditis, and meningism). These side effects may be life-threatening and can be reduced by coadministration of corticosteroids. All patients with cerebral cysticercosis are strongly recommended to be hospitalized during treatment.
  • Gastrointestinal tract: About 90% of all patients have abdominal pain or cramps with or without nausea and vomiting. Diarrhea may develop and may be severe with colic. Sweating, fever, and sometimes bloody stools may occur together with diarrhea.
  • Liver: Asymptomatic and transient increases of liver enzymes (AST and ALT) are noted frequently (up to 27%). No case of symptomatic liver damage has been seen so far.
  • Sensitivity reactions: Urticaria, rash, pruritus and eosinophilia in white blood cell counts
  • Other locations/body as a whole: Lower back pain, myalgia, arthralgia, fever, sweating, various cardiac arrhythmias, and hypotension

Pregnancy

The WHO states praziquantel is safe during pregnancy.[14] Animal studies have failed to reveal evidence of fetal harm. Praziquantel is effective in reducing schistosomiasis during pregnancy.[15] Another trial found that treatment with praziquantel did not increase the rates of low birthweight, fetal death, or congenital anomalies.[16]

Drug interactions

The antibiotic rifampicin decreases plasma concentrations of praziquantel.[17]

Carbamazepine and phenytoin are reported to reduce the bioavailability of praziquantel.[18] Chloroquine also reduces its bioavailability.[19]

The drug cimetidine heightens praziquantel bioavailability.[20][21]

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.[citation needed]

Another hypothesis regarding the mechanism of action is that it interferes with adenosine uptake in worms.[22] 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.[citation needed]

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."[23]

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.[24]

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.[citation needed]

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.[9]

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.[citation needed]

Society and culture

Brand names

  • Biltricide (Bayer) Tablets (for human use)[25]
  • Cesol (Merck) Tablets
  • Cestoved (Vedco) both tablets and injectable for veterinary use
  • Cysticide (Merck) Tablets
  • Distocide (Shin Poong Pharm. Co., Ltd.) tablet (for human use)
  • Distoside (Chandra Bhagat Pharma Pvt Ltd) tablet (for human use)
  • Droncit (Bayer) for veterinary use
  • Drontal (combination with pyrantel pamoate) (Bayer) for veterinary use
  • D-Worm (Farnum) for veterinary use; note that D-Worm also makes roundworm medicine containing piperidine which is not effective against tapeworms.
  • Fish Tapes (Thomas Labs) for aquarium use
  • Interceptor Plus chewable tablets (combination with milbemycin) (Elanco) for veterinary use. Note regular Interceptor only has milbemycin and does not contain praziquantel.
  • Kaicide (Taiwan)
  • Milbemax (combination with milbemycin oxime) (Novartis) for veterinary use
  • Popantel (Jurox)
  • PraziPro (Hikari) for aquarium use
  • Praz-Tastic (NFP/National Fish Pharmaceuticals) for aquarium use
  • Pure Prazi (COTS Koi/Children of the Sun Koi) for aquarium use
  • PraziPure (J.K.O., Inc. d/b/a Kodama Koi Farm & Kodama Koi Garden; licensed by COTS Koi) for aquarium use
  • Profender (combination with emodepside) (Bayer) for veterinary use
  • Tape Worm Tabs (Trade Winds) for veterinary use
  • Zentozide (Berich (Thailand) Co)

Regulatory approval

Praziquantel is on the World Health Organization's List of Essential Medicines.[4]

Praziquantel is not licensed for use in humans in the UK, but it can be imported when necessary on a named-patient basis.[26] 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.[27]

Veterinary medicine

It may cause problems in dogs with MDR1 mutations.[29]

See also

References

  1. ↑ "Farnam Pet Press Release. TRUSTED D-WORM offers product for tapeworm management". Farnam Companies, Inc.. http://www.farnampet.com/press_releases.php?id=100674. 
  2. ↑ 2.0 2.1 2.2 2.3 2.4 2.5 "Praziquantel". The American Society of Health-System Pharmacists. https://www.drugs.com/monograph/praziquantel.html. 
  3. ↑ 3.0 3.1 3.2 WHO Model Formulary 2008. World Health Organization. 2009. pp. 88, 593. ISBN 9789241547659. 
  4. ↑ 4.0 4.1 World Health Organization model list of essential medicines: 21st list 2019. Geneva: World Health Organization. 2019. WHO/MVP/EMP/IAU/2019.06. License: CC BY-NC-SA 3.0 IGO. 
  5. ↑ "Albendazole versus praziquantel in the treatment of neurocysticercosis: a meta-analysis of comparative trials". PLOS Neglected Tropical Diseases 2 (3): e194. March 2008. doi:10.1371/journal.pntd.0000194. PMID 18335068. 
  6. ↑ 6.0 6.1 6.2 Drontal Data Sheet; Drontal Cat & Cat XL Film-coated Tablets, Bayer plc, Newbury, England: Bayer plc, Animal Health Division, p. 2, https://www.drontal.com/static/drontal/DrontalCat&CatXLFilm-coatedTablets.pdf, retrieved 23 September 2015 
  7. ↑ 7.0 7.1 Feline clinical parasitology (First ed.). Ames, Iowa: Iowa State University. 2002. p. 275. ISBN 0-8138-0333-0. https://books.google.com/books?id=mvpsA9dGdpAC&q=%22toxocara+cati%22&pg=PA278. 
  8. ↑ "Efficacy of praziquantel against Schistosoma haematobium infection in children". The American Journal of Tropical Medicine and Hygiene 71 (6): 778–782. December 2004. doi:10.4269/ajtmh.2004.71.778. PMID 15642971. 
  9. ↑ 9.0 9.1 The Carter Center. "Schistosomiasis Control Program". http://www.cartercenter.org/health/schistosomiasis/index.html. 
  10. ↑ "Collection of Clonorchis sinensis adult worms from infected humans after praziquantel treatment". The Korean Journal of Parasitology 45 (2): 149–152. June 2007. doi:10.3347/kjp.2007.45.2.149. PMID 17570980. PMC 2526309. http://www.parasitol.or.kr/kjp/abstracts/2007_149.html. 
  11. ↑ "CDC - Paragonimiasis - General Information - Frequently Asked Questions (FAQs)" (in en-us). 2019-04-19. https://www.cdc.gov/parasites/paragonimus/gen_info/faqs.html. 
  12. ↑ "CDC - Paragonimiasis - Resources for Health Professionals" (in en-us). 2019-05-24. https://www.cdc.gov/parasites/paragonimus/health_professionals/index.html. 
  13. ↑ "Fascioliasis and other plant-borne trematode zoonoses". International Journal for Parasitology 35 (11–12): 1255–1278. October 2005. doi:10.1016/j.ijpara.2005.07.010. PMID 16150452. 
  14. ↑ "WHO | Strategy". https://www.who.int/schistosomiasis/strategy/en/. 
  15. ↑ "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. doi:10.1186/1471-2334-9-32. PMID 19296834. 
  16. ↑ "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. doi:10.1016/S1473-3099(15)00345-X. PMID 26511959. 
  17. ↑ "Rifampin markedly decreases plasma concentrations of praziquantel in healthy volunteers". Clinical Pharmacology and Therapeutics 72 (5): 505–513. November 2002. doi:10.1067/mcp.2002.129319. PMID 12426514. 
  18. ↑ "Drug interactions of clinical importance. An updated guide". Drug Safety 12 (6): 393–452. June 1995. doi:10.2165/00002018-199512060-00005. PMID 8527014. 
  19. ↑ "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. doi:10.1002/bdd.2510150103. PMID 8161714. 
  20. ↑ "Effect of cimetidine, bicarbonate and glucose on the bioavailability of different formulations of praziquantel". Arzneimittel-Forschung 45 (4): 516–518. April 1995. PMID 7779153. 
  21. ↑ "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. doi:10.1128/AAC.41.6.1256. PMID 9174180. 
  22. ↑ "The anti-schistosomal drug praziquantel is an adenosine antagonist". Parasitology 134 (Pt 9): 1215–1221. August 2007. doi:10.1017/S0031182007002600. PMID 17428352. 
  23. ↑ "Archived copy". http://bayer.naccvp.com/view_label.php. [full citation needed]
  24. ↑ "Resolution of praziquantel". PLOS Neglected Tropical Diseases 5 (9): e1260. September 2011. doi:10.1371/journal.pntd.0001260. PMID 21949890. 
  25. ↑ "BILTRICIDE- praziquantel tablet, film coated (NDC Code(s): 50419-747-01)". July 2015. http://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=34ce1cdd-648e-4f1e-8512-bf3d4cc22eb9. 
  26. ↑ "Antihelmintics - Medicines for Worms; threadword, roundworm". Patient. http://patient.info//health/antihelmintics-medicines-for-worms. 
  27. ↑ Goodman and Gilman's The Pharmacological Basis of Therapeutics, Twelfth Edition (12 ed.). New York: McGraw-Hill Education / Medical. 2011-01-10. ISBN 9780071624428. [page needed]
  28. ↑ "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. doi:10.1007/bf00531089. PMID 3615395. 
  29. ↑ "List of Drugs That Cause Sensitivity to Dogs With mdr1 Mutation". www.collieassociation.co.uk. http://www.collieassociation.co.uk/health/MDR1leaflet.pdf. 

External links



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