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Praziquantel

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Praziquantel
Clinical data
Pronunciation/ˌpræzɪˈkwɒntɛl/
Trade namesBiltricide
AHFS/Drugs.comMonograph
MedlinePlusa608048
License data
Pregnancy
category
  • AU: B1
Routes of
administration		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)
ExcretionKidney (mainly)
Identifiers
  • (RS)-2-(Cyclohexylcarbonyl)-1,2,3,6,7,11b-hexahydro-4H-pyrazino[2,1-a]isoquinolin-4-one
CAS Number
PubChem CID
DrugBank
ChemSpider
UNII
KEGG
ChEMBL
CompTox Dashboard (EPA)
ECHA InfoCard100.054.126 Edit this at Wikidata
Chemical and physical data
FormulaC19H24N2O2
Molar mass312.413 g·mol−1
3D model (JSmol)
Melting point136 to 138 °C (277 to 280 °F)
  • O=C4N2C(c1c(cccc1)CC2)CN(C(=O)C3CCCCC3)C4
  • InChI=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 checkY
  • Key:FSVJFNAIGNNGKK-UHFFFAOYSA-N checkY
  (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.[3] In humans specifically, it is used to treat schistosomiasis, clonorchiasis, opisthorchiasis, tapeworm infections, cysticercosis, echinococcosis, paragonimiasis, fasciolopsiasis, and fasciolosis.[3] It should not be used for worm infections of the eye.[4] It is taken by mouth.[3]

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

Praziquantel was approved for medical use in the United States in 1982.[3] It is on the World Health Organization's List of Essential Medicines.[5]

Medical uses

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

Side effects

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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

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The WHO states praziquantel is safe during pregnancy (although does not recommend use during the first trimester).[22] [23] Animal studies have failed to reveal evidence of fetal harm. Praziquantel is effective in reducing schistosomiasis during pregnancy.[24] Another trial found that treatment with praziquantel did not increase the rates of low birthweight, fetal death, or congenital anomalies.[25]

Drug interactions

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The antibiotic rifampicin decreases plasma concentrations of praziquantel.[26]

Carbamazepine and phenytoin are reported to reduce the bioavailability of praziquantel.[27] Chloroquine also reduces its bioavailability.[28]

The drug cimetidine heightens praziquantel bioavailability.[29][30]

Mechanism of action

[edit]

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.[31] 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."[32]

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.[33]

Pharmacokinetics

[edit]

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.[14]

History

[edit]

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

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Brand names

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  • Biltricide (Bayer) Tablets (for human use)[34]
  • 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

[edit]

Praziquantel is on the World Health Organization's List of Essential Medicines.[5]

Praziquantel is not licensed for use in humans in the UK, but it can be imported when necessary on a named-patient basis.[35] 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.[36]

Veterinary medicine

[edit]

It may cause problems in dogs with MDR1 mutations.[38]

See also

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References

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  1. ^ "Product monograph brand safety updates". Health Canada. February 2024. Retrieved 24 March 2024.
  2. ^ "Farnam Pet Press Release. TRUSTED D-WORM offers product for tapeworm management". Farnam Companies, Inc. Archived from the original on 14 October 2008. Retrieved 3 October 2016.
  3. ^ a b c d e f "Praziquantel". The American Society of Health-System Pharmacists. Archived from the original on 20 December 2016. Retrieved 8 December 2016.
  4. ^ a b c World Health Organization (2009). Stuart MC, Kouimtzi M, Hill SR (eds.). WHO Model Formulary 2008. World Health Organization. pp. 88, 593. hdl:10665/44053. ISBN 9789241547659.
  5. ^ a b World Health Organization (2019). World Health Organization model list of essential medicines: 21st list 2019. Geneva: World Health Organization. hdl:10665/325771. WHO/MVP/EMP/IAU/2019.06. License: CC BY-NC-SA 3.0 IGO.
  6. ^ Matthaiou DK, Panos G, Adamidi ES, Falagas ME (March 2008). Carabin H (ed.). "Albendazole versus praziquantel in the treatment of neurocysticercosis: a meta-analysis of comparative trials". PLOS Neglected Tropical Diseases. 2 (3): e194. doi:10.1371/journal.pntd.0000194. PMC 2265431. PMID 18335068.
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  21. ^ Taraschewski H, Mehlhorn H, Bunnag D, Andrews P, Thomas H (November 1986). "Effects of praziquantel on human intestinal flukes (Fasciolopsis buski and Heterophyes heterophyes)". Zentralblatt für Bakteriologie, Mikrobiologie und Hygiene. Series A: Medical Microbiology, Infectious Diseases, Virology, Parasitology. 262 (4): 542–550. doi:10.1016/s0176-6724(86)80148-1. PMID 3799097.
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  29. ^ Metwally A, Bennett JL, Botros S, Ebeid F (April 1995). "Effect of cimetidine, bicarbonate and glucose on the bioavailability of different formulations of praziquantel". Arzneimittel-Forschung. 45 (4): 516–518. PMID 7779153.
  30. ^ Jung H, Medina R, Castro N, Corona T, Sotelo J (June 1997). "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. doi:10.1128/AAC.41.6.1256. PMC 163896. PMID 9174180.
  31. ^ Angelucci F, Basso A, Bellelli A, Brunori M, Pica Mattoccia L, Valle C (August 2007). "The anti-schistosomal drug praziquantel is an adenosine antagonist". Parasitology. 134 (Pt 9): 1215–1221. doi:10.1017/S0031182007002600. PMID 17428352. S2CID 22482704.
  32. ^ "Archived copy". Archived from the original on 2007-05-18. Retrieved 2010-03-24.{{cite web}}: CS1 maint: archived copy as title (link)[full citation needed]
  33. ^ Woelfle M, Seerden JP, de Gooijer J, Pouwer K, Olliaro P, Todd MH (September 2011). Geary TG (ed.). "Resolution of praziquantel". PLOS Neglected Tropical Diseases. 5 (9): e1260. doi:10.1371/journal.pntd.0001260. PMC 3176743. PMID 21949890.
  34. ^ "BILTRICIDE- praziquantel tablet, film coated (NDC Code(s): 50419-747-01)". DailyMed. July 2015. Archived from the original on 2015-09-10. Retrieved 2015-09-08.
  35. ^ "Antihelmintics - Medicines for Worms; threadword, roundworm". Patient. Archived from the original on 2015-06-18. Retrieved 2015-06-15.
  36. ^ Brunton L, Chabner B, Knollman B (2011-01-10). Goodman and Gilman's The Pharmacological Basis of Therapeutics, Twelfth Edition (12 ed.). New York: McGraw-Hill Education / Medical. ISBN 9780071624428.[page needed]
  37. ^ Schmahl G, Taraschewski H (1987). "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. doi:10.1007/bf00531089. PMID 3615395. S2CID 12241452.
  38. ^ "List of Drugs That Cause Sensitivity to Dogs With mdr1 Mutation" (PDF). www.collieassociation.co.uk. Archived (PDF) from the original on 2016-07-05. Retrieved 2016-06-05.
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