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Praziquantel

Systematic (IUPAC) name

(RS)-2-(Cyclohexylcarbonyl)-1,2,3,6,7,11b-hexahydro-4H-pyrazino[2,1-

a]isoquinolin-4-one

Clinical data

Trade names Biltricide

AHFS/Drugs.com monograph

MedlinePlus a608048

Pregnancy cat. Only when clearly needed (lack of sufficient

data in humans)

Legal status U.S.: Rx-only (human use), over-the-counter

(veterinary use)[1]

(http://www.farnampet.com/press_releases.php?

id=100674)

Routes oral

Pharmacokinetic data

Bioavailability relatively small

PraziquantelFrom Wikipedia, the free encyclopedia

Praziquantel (Biltricide) is ananthelmintic effective against flatworms.Praziquantel is not licensed for use inhumans in the UK; it is, however, availableas a veterinary anthelmintic, and isavailable for use in humans on a named-patient basis.

Contents

1 Uses

2 History3 Pharmacokinetics

4 Mode of action5 Side effects

6 Drug interactions

6.1 Antibiotics6.2 Antiepileptics

6.3 Antimalarials

6.4 Antacids / histamine

H2-antagonists

7 Dosage8 Brand names

9 References

Uses

Praziquantel is used to treat diseases inhumans, mammals, and fish that are causedby infection with several types of internal/gastrointestinal, and external parasitesincluding the following:

Salmon poisoning disease

Hydatid disease caused by infection

of various organs with larval stages

of tapeworms of the genus

Echinococcus

Cysticercosis caused by infection of

the brain and/ or muscles with the

eggs and larvae of the pork

tapeworm Taenia solium (though it

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Metabolism hepatic

Half-life 0.8 to 1.5 hours (Main Metabolites 4 to 5 hours)

Excretion mainly in urine

Identifiers

CAS number 55268-74-1

ATC code P02BA01 QP52AA01

PubChem CID 4891

DrugBank DB01058

ChemSpider 4722

UNII 6490C9U457

KEGG D00471

ChEMBL CHEMBL976

Chemical data

Formula C19H24N2O2

Mol. mass 312.411

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has been judged less effective thanalbendazole in treatment of

neurocysticercosis)[1]

Feline taeniasis caused in cats by

gastrointestinal infection with adult

tapeworms of the species Taenia

taeniaeformis; used either alone or

in combination with pyrantel

pamoate

Toxocariasis in cats and dogs

whose gut is infected with theroundworms/ nematodes Toxocara

cati or Toxocara canis

respectively; use is often combined

with pyrantel [2]

Schistosomiasis caused by

trematodes of the genus

Schistosoma.[3] As of 2005,

praziquantel is the primary treatmentfor human schistosomiasis, for which

it is usually effective in a single

dose.[4]

Clonorchiasis brought on by theChinese liver fluke Clonorchis

sinensis[5]

Paragonimiasis caused by infection with lung flukes, mostly of the species Paragonimus

westermani.[citation needed]

Fasciolopsiasis caused by intestinal fluke Fasciolopsis buski[6]

Diplozoon paradoxum and other Trematoda infections of many fish species. [7]

History

Praziquantel was developed in the laboratories for parasitological research of Bayer AG and Merck KGaA inGermany (Elberfeld and Darmstadt) in the mid 1970s. The World Health Organization includes it on its ModelList of Essential Medicines.

Pharmacokinetics

Praziquantel is well absorbed (approximately 80%) from the gastrointestinal tract. However, due to extensivefirst-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 classes B ll///d C), the serum half-life is increasedto 3 to 8 hours. Praziquantel and its metabolites are mainly excreted renally; within 24 hours after a single oraldose, 70 to 80% is found in urine, but less than 0.1% as the unchanged drug. Praziquantel is metabolizedthrough 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.

SMILES

InChI

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Praziquantel has a particularly dramatic effect on patients with schistosomiasis. Studies of those treated haveshown 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.[4]

Mode of action

Although the mode of action is not exactly known at present, there is experimental evidence that praziquantelincreases the permeability of the membranes of schistosome cells towards calcium ions. The drug therebyinduces contraction of the parasites, resulting in paralysis in the contracted state. The dying parasites aredislodged from their site of action in the host organism and may enter systemic circulation or may be destroyedby host immune reaction (phagocytosis). Additional mechanisms including focal disintegrations and disturbancesof oviposition (laying of eggs) are seen in other types of sensitive parasites.

Another hypothesis concerning the mechanism of action of praziquantel has been recently reported. The drugseems to interfere with adenosine uptake in cultured worms. This effect may have therapeutical relevance giventhat the schistosome, as the taenia and the echinococcus (other praziquantel sensitive parasites), is unable tosynthesize 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 fromthe bile, cestocidal activity is exhibited. Following exposure to praziquantel, the tapeworm loses its ability toresist 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 andpartially digested pieces of tapeworms will be seen in the stool. The majority of tapeworms are digested and are

not found in the feces."[8]

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.[9]

Side effects

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

Central nervous system: 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. It is strongly recommendedthat all patients with cerebral cysticercosis are hospitalized during treatment.

GI Tract: Approximately 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 ever been seen so far.

Sensitivity reactions: Urticaria, rash, pruritus and eosinophilia in white blood cell countsOther locations/body as a whole: Lower back pain, myalgia, arthralgia, fever, sweating, various cardiac

arrhythmias, and hypotension

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Drug interactions

Antibiotics

A study found that the antibiotic rifampicin decreases plasma concentrations of praziquantel.[10]

Antiepileptics

Carbamazepine and phenytoin are reported to reduce the bioavailability of praziquantel.[11]

Antimalarials

Chloroquine reduces the bioavailability of praziquantel.[12]

Antacids / histamine H2-antagonists

At least 2 studies indicate the drug cimetidine heightens praziquantel bioavailability.[13][14]

Dosage

For schistosomiasis, the dose is 20 milligrams/kilogram by mouth every 4–6 hours for one day. For tapeworms,the dose is 5–25 mg/kg by mouth once. For liver fluke, the dose is 25 mg/kg by mouth every 4–6 hours for oneday. These dosages are for patients over 4 years old, and are to be taken with food or a few minutes before ameal.

Brand names

Biltricide (Bayer) 600 mg Tablets (for human use)

Cesol (Merck) Tablets

Cestoved (Vedco) both tablets and injectable for veterinary use

Cysticide (Merck) TabletsDistoside (Chandra Bhagat Pharma Pvt Ltd) 600mg tablet (for human use)

Droncit (Bayer) for veterinary use

Drontal (combination with pyrantel pamoate) (Bayer) for veterinary useD-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

Profender (combination with emodepside) (Bayer) for veterinary useTape Worm Tabs (Trade Winds) for veterinary use

Zentozide (Berich (Thailand) Co)

References

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1. ^ Matthaiou DK, Panos G, Adamidi ES, Falagas ME (2008). "Albendazole versus Praziquantel in the Treatmentof Neurocysticercosis: A Meta-analysis of Comparative Trials"(http://www.plosntds.org/article/info:doi/10.1371/journal.pntd.0000194). In Carabin, Hélène. PLoS Negl Trop

Dis 2 (3): e194. doi:10.1371/journal.pntd.0000194 (http://dx.doi.org/10.1371%2Fjournal.pntd.0000194).PMC 2265431 (//www.ncbi.nlm.nih.gov/pmc/articles/PMC2265431). PMID 18335068(//www.ncbi.nlm.nih.gov/pubmed/18335068).

2. ^ Bowman, Dwight D.; Hendrix, Charles M.; Lindsay, David S.; Barr, Steven C. (2002). Feline clinicalparasitology (http://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) (Firsted.). Ames, Iowa: Iowa State University. p. 275. ISBN 0-8138-0333-0.

3. ^ Tchuenté LA, Shaw DJ, Polla L, Cioli D, Vercruysse J (December 2004). "Efficacy of praziquantel againstSchistosoma haematobium infection in children" (http://www.ajtmh.org/cgi/pmidlookup?

view=long&pmid=15642971). Am. J. Trop. Med. Hyg. 71 (6): 778–82. PMID 15642971(//www.ncbi.nlm.nih.gov/pubmed/15642971).

4. ̂a b The Carter Center. "Schistosomiasis Control Program"(http://www.cartercenter.org/health/schistosomiasis/index.html). Retrieved 2008-07-17.

5. ^ Shen C, Kim J, Lee JK, et al. (June 2007). "Collection of Clonorchis sinensis adult worms from infectedhumans after praziquantel treatment" (http://www.parasitol.or.kr/kjp/abstracts/2007_149.html). The Korean

Journal of Parasitology 45 (2): 149–52. doi:10.3347/kjp.2007.45.2.149(http://dx.doi.org/10.3347%2Fkjp.2007.45.2.149). PMC 2526309(//www.ncbi.nlm.nih.gov/pmc/articles/PMC2526309). PMID 17570980(//www.ncbi.nlm.nih.gov/pubmed/17570980).

6. ^ 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(http://dx.doi.org/10.1016%2Fj.ijpara.2005.07.010). PMID 16150452(//www.ncbi.nlm.nih.gov/pubmed/16150452).

7. ^ "Treatment of fish parasites. 2. Effects of praziquantel, niclosamide, levamisole-HCl, and metrifonate onmonogenea (Gyrodactylus aculeati, Diplozoon paradoxum)" (http://www.ncbi.nlm.nih.gov/pubmed/3615395).

8. ^ http://bayer.naccvp.com/view_label.php

9. ^ Woelfle, M.; Seerden, J. P.; De Gooijer, J.; Pouwer, K.; Olliaro, P.; Todd, M. H. (2011). "Resolution ofPraziquantel" (http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3176743). In Geary, Timothy G. PLoS Neglected

Tropical Diseases 5 (9): e1260. doi:10.1371/journal.pntd.0001260(http://dx.doi.org/10.1371%2Fjournal.pntd.0001260). PMC 3176743(//www.ncbi.nlm.nih.gov/pmc/articles/PMC3176743). PMID 21949890(//www.ncbi.nlm.nih.gov/pubmed/21949890).

10. ^ 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 (http://dx.doi.org/10.1067%2Fmcp.2002.129319).PMID 12426514 (//www.ncbi.nlm.nih.gov/pubmed/12426514).

11. ^ 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 (http://dx.doi.org/10.2165%2F00002018-199512060-00005). PMID 8527014 (//www.ncbi.nlm.nih.gov/pubmed/8527014).

12. ^ 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 (http://dx.doi.org/10.1002%2Fbdd.2510150103). PMID 8161714(//www.ncbi.nlm.nih.gov/pubmed/8161714).

13. ^ 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 (//www.ncbi.nlm.nih.gov/pubmed/7779153).

14. ^ Jung H, Medina R, Castro N, Corona T, Sotelo J (June 1997). "Pharmacokinetic study of praziquanteladministered alone and in combination with cimetidine in a single-day therapeutic regimen"

(http://aac.asm.org/cgi/pmidlookup?view=long&pmid=9174180). Antimicrob. Agents Chemother. 41 (6): 1256–9. PMC 163896 (//www.ncbi.nlm.nih.gov/pmc/articles/PMC163896). PMID 9174180(//www.ncbi.nlm.nih.gov/pubmed/9174180).

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