Praziquantel

Praziquantel
Names
Pronunciation/ˌpræzɪˈkwɒntɛl/
Trade namesBiltricide[1]
IUPAC name
  • (RS)-2-(Cyclohexylcarbonyl)-1,2,3,6,7,11b-hexahydro-4H-pyrazino[2,1-a]isoquinolin-4-one
Clinical data
Drug classAntihelminthic[2]
Main usesSchistosomiasis, clonorchiasis, opisthorchiasis, tapeworm infections, cysticercosis, hydatid disease, other fluke infections[2]
Side effectsPoor coordination, abdominal pain, vomiting, headache, allergic reactions[3]
WHO AWaReUnlinkedWikibase error: ⧼unlinkedwikibase-error-statements-entity-not-set⧽
Pregnancy
category
  • AU: B1
  • US: B (No risk in non-human studies)
    Routes of
    use    		Human use: by mouth (tablets)[4]
    Defined daily dose3 grams[5]
    External links
    AHFS/Drugs.comMonograph
    MedlinePlusa608048
    Legal
    License data
    Legal status
    Pharmacokinetics
    BioavailabilityRelatively small
    MetabolismLiver[4]
    Elimination half-life1.0–1.5 hours[4] (main metabolites: 4–5 hours)
    ExcretionUrine (mainly)[4]
    Chemical and physical data
    FormulaC19H24N2O2
    Molar mass312.413 g·mol−1
    3D model (JSmol)
    Melting point136 to 138 °C (277 to 280 °F)
    SMILES
    • O=C4N2C(c1c(cccc1)CC2)CN(C(=O)C3CCCCC3)C4
    InChI
    • 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

    Praziquantel (PZQ), sold under the brandname Biltricide among others, is a medication used to treat a number of types of parasitic worm infections.[2] Specifically, it is used for schistosomiasis, clonorchiasis, opisthorchiasis, tapeworm infections, cysticercosis, hydatid disease, and other fluke infections.[2] It should not be used for worm infections of the eye.[3] It is taken by mouth.[4]

    Side effects 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.[7] The wholesale cost in the developing world is about US$0.4–18.15 per day.[8] In the United States a typical course of treatment costs $100–200.[9]

    Medical uses

    Sparganosis initially presented as recurrent pericardial effusion a) Radiograph b) echocardiogram after praziquantel, no evidence of pericardia or pleural effusion.[10]

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

    Dosage

    Praziquantel

    The defined daily dose is 3 grams (by mouth).[5]

    T. saginata, T. solium, and D. latum are treated with a single dose of 5 to 10 mg/kg.[20] Fluke infections are treated with 25 mg/kg three times per day for one day if the intestines are involved and two days if the lungs or liver is involved.[20] For schistosomiasis either two or three doses four hours apart of 20 mg/kg may be used.[20]

    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.

    • 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.[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 interfere 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.[15]

    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

    • Biltricide (Bayer) Tablets (for human use)[32]
    • 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
    • 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.[7]

    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

    References

    1. ↑ "HIGHLIGHTS OF PRESCRIBING; BILTRICIDE (praziquantel) tablets, for oral useFORMATION:" (PDF). www.accessdata.fda.gov. Archived (PDF) from the original on 1 April 2021. Retrieved 13 October 2021.
    2. 1 2 3 4 5 6 7 "Praziquantel". The American Society of Health-System Pharmacists. Archived from the original on 20 December 2016. Retrieved 8 December 2016.
    3. 1 2 3 4 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.
    4. 1 2 3 4 5 Ritter, James M.; Flower, Rod; Henderson, Graeme; Loke, Yoon Kong; Rang, Humphrey P. (2020). "56. Antihelminthic drugs". Rang & Dale's Pharmacology. Elsevier. pp. 710–715. ISBN 978-0-7020-7448-6. Archived from the original on 2021-08-28. Retrieved 2021-10-12.
    5. 1 2 "WHOCC - ATC/DDD Index". www.whocc.no. Archived from the original on 19 September 2020. Retrieved 21 September 2020.
    6. ↑ "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.
    7. 1 2 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.
    8. ↑ "Praziquantel". International Drug Price Indicator Guide. Archived from the original on 22 January 2018. Retrieved 8 December 2016.
    9. ↑ Hamilton, Richart (2015). Tarascon Pocket Pharmacopoeia 2015 Deluxe Lab-Coat Edition. Jones & Bartlett Learning. p. 54. ISBN 9781284057560.
    10. ↑ Liu, Dongyou (5 July 2012). Molecular Detection of Human Parasitic Pathogens. CRC Press. p. 291. ISBN 978-1-4398-1243-3. Archived from the original on 25 February 2022. Retrieved 24 February 2022.
    11. ↑ Matthaiou DK, Panos G, Adamidi ES, Falagas ME (2008). Carabin H (ed.). "Albendazole versus Praziquantel in the Treatment of Neurocysticercosis: A Meta-analysis of Comparative Trials". PLOS Negl Trop Dis. 2 (3): e194. doi:10.1371/journal.pntd.0000194. PMC 2265431. PMID 18335068.
    12. 1 2 3 Drontal Data Sheet; Drontal Cat & Cat XL Film-coated Tablets, Bayer plc (PDF), Newbury, England: Bayer plc, Animal Health Division, p. 2, archived (PDF) from the original on 23 September 2015, retrieved 23 September 2015
    13. 1 2 Bowman, Dwight D.; Hendrix, Charles M.; Lindsay, David S.; Barr, Steven C. (2002). Feline clinical parasitology (First ed.). Ames, Iowa: Iowa State University. p. 275. ISBN 0-8138-0333-0. Archived from the original on 2017-09-10.
    14. ↑ Tchuenté LA, Shaw DJ, Polla L, Cioli D, Vercruysse J (December 2004). "Efficacy of praziquantel against Schistosoma haematobium infection in children". Am. J. Trop. Med. Hyg. 71 (6): 778–82. doi:10.4269/ajtmh.2004.71.778. PMID 15642971. Archived (PDF) from the original on 2020-04-08. Retrieved 2008-12-19.
    15. 1 2 The Carter Center. "Schistosomiasis Control Program". Archived from the original on 2008-07-20. Retrieved 2008-07-17.
    16. ↑ Shen C, Kim J, Lee JK, et al. (June 2007). "Collection of Clonorchis sinensis adult worms from infected humans after praziquantel treatment". The Korean Journal of Parasitology. 45 (2): 149–52. doi:10.3347/kjp.2007.45.2.149. PMC 2526309. PMID 17570980. Archived from the original on 2012-12-20.
    17. ↑ "CDC - Paragonimiasis - General Information - Frequently Asked Questions (FAQs)". www.cdc.gov. 2019-04-19. Archived from the original on 2019-10-02. Retrieved 2019-10-02.
    18. ↑ "CDC - Paragonimiasis - Resources for Health Professionals". www.cdc.gov. 2019-05-24. Archived from the original on 2019-10-02. Retrieved 2019-10-02.
    19. ↑ Mas-Coma S, Bargues MD, Valero MA (October 2005). "Fascioliasis and other plant-borne trematode zoonoses". Int. J. Parasitol. 35 (11–12): 1255–78. doi:10.1016/j.ijpara.2005.07.010. PMID 16150452.
    20. 1 2 3 "PRAZIQUANTEL oral - Essential drugs". medicalguidelines.msf.org. Archived from the original on 28 August 2021. Retrieved 23 August 2020.
    21. ↑ "WHO | Strategy". World Health Organisation: Schistosomiasis. Archived from the original on 14 July 2020. Retrieved 4 March 2020.
    22. ↑ Tweyongyere, Robert; Mawa, Patrice A; Elliott, Alison M (18 March 2009). "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. doi:10.1186/1471-2334-9-32. PMC 2666740. PMID 19296834.
    23. ↑ Olveda, Remigio M; Acosta, Luz P; Friedman, Jennifer F (February 2016). "A randomized double blind placebo controlled trial assessing the efficacy and safety of praziquantel for the treatment of human schistosomiasis during pregnancy". The Lancet. Infectious Diseases. 16 (2): 199–208. doi:10.1016/S1473-3099(15)00345-X. PMC 4752899. PMID 26511959.
    24. ↑ Ridtitid W, Wongnawa M, Mahatthanatrakul W, Punyo J, Sunbhanich M (November 2002). "Rifampin markedly decreases plasma concentrations of praziquantel in healthy volunteers". Clin. Pharmacol. Ther. 72 (5): 505–13. doi:10.1067/mcp.2002.129319. PMID 12426514.
    25. ↑ Quinn DI, Day RO (June 1995). "Drug interactions of clinical importance. An updated guide". Drug Saf. 12 (6): 393–452. doi:10.2165/00002018-199512060-00005. PMID 8527014.
    26. ↑ Masimirembwa CM, Naik YS, Hasler JA (January 1994). "The effect of chloroquine on the pharmacokinetics and metabolism of praziquantel in rats and in humans". Biopharm Drug Dispos. 15 (1): 33–43. doi:10.1002/bdd.2510150103. PMID 8161714.
    27. ↑ Metwally A, Bennett JL, Botros S, Ebeid F (April 1995). "Effect of cimetidine, bicarbonate and glucose on the bioavailability of different formulations of praziquantel". Arzneimittelforschung. 45 (4): 516–8. PMID 7779153.
    28. ↑ 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". Antimicrob. Agents Chemother. 41 (6): 1256–9. doi:10.1128/AAC.41.6.1256. PMC 163896. PMID 9174180.
    29. ↑ 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 (9): 1215–1221. doi:10.1017/S0031182007002600. ISSN 0031-1820. PMID 17428352.
    30. ↑ "Archive copy". Archived from the original on 2007-05-18. Retrieved 2010-03-24.{{cite web}}: CS1 maint: archived copy as title (link)
    31. ↑ Woelfle, M.; Seerden, J. P.; De Gooijer, J.; Pouwer, K.; Olliaro, P.; Todd, M. H. (2011). Geary, Timothy G (ed.). "Resolution of Praziquantel". PLOS Neglected Tropical Diseases. 5 (9): e1260. doi:10.1371/journal.pntd.0001260. PMC 3176743. PMID 21949890.
    32. ↑ "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.
    33. ↑ "Antihelmintics - Medicines for Worms; threadword, roundworm". Patient. Archived from the original on 2015-06-18. Retrieved 2015-06-15.
    34. ↑ Brunton, Laurence; Chabner, Bruce; Knollman, Bjorn (2011-01-10). Goodman and Gilman's The Pharmacological Basis of Therapeutics, Twelfth Edition (12 ed.). New York: McGraw-Hill Education / Medical. ISBN 9780071624428.
    35. ↑ Schmahl G, Taraschewski H (1987). "Treatment of fish parasites. 2. Effects of praziquantel, niclosamide, levamisole-HCl, and metrifonate on monogenea (Gyrodactylus aculeati, Diplozoon paradoxum)". Parasitol Res. 73 (4): 341–51. doi:10.1007/bf00531089. PMID 3615395.
    36. ↑ "Archived copy" (PDF). Archived (PDF) from the original on 2016-07-05. Retrieved 2016-06-05.{{cite web}}: CS1 maint: archived copy as title (link)


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