Praziquantel

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Praziquantel
Praziquantel.svg
Praziquantel.gif
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]
Routes oral
Pharmacokinetic data
Bioavailability relatively small
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 YesY
ATC code P02BA01 QP52AA01
PubChem CID 4891
DrugBank DB01058
ChemSpider 4722 YesY
UNII 6490C9U457 YesY
KEGG D00471 YesY
ChEMBL CHEMBL976 YesY
Chemical data
Formula C19H24N2O2 
Mol. mass 312.411
 YesY (what is this?)  (verify)

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

Uses[edit]

Praziquantel is used to treat diseases in humans, mammals, and fish that are caused by infection with several types of internal/ gastrointestinal, and external parasites including the following:

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. The World Health Organization includes it on its Model List of Essential Medicines.

Pharmacokinetics[edit]

Praziquantel is well absorbed (approximately 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 classes B ll///d C), the serum half-life is increased to 3 to 8 hours. Praziquantel and its metabolites are mainly excreted renally; within 24 hours 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.[4]

Mechanism of action[edit]

The mode of action is not exactly known at present, there is experimental evidence that praziquantel increases the permeability of the membranes of schistosome cells towards calcium ions. The drug thereby induces contraction of the parasites, 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 concerning the mechanism of action of praziquantel has been recently reported. The drug seems to interfere with adenosine uptake in cultured worms. 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."[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[edit]

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: 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 recommended that 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 counts
  • Other locations/body as a whole: Lower back pain, myalgia, arthralgia, fever, sweating, various cardiac arrhythmias, and hypotension

Drug interactions[edit]

Antibiotics[edit]

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

Antiepileptics[edit]

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

Antimalarials[edit]

Chloroquine reduces the bioavailability of praziquantel.[12]

Antacids / histamine H2-antagonists[edit]

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

Dosage[edit]

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 one day. These dosages are for patients over 4 years old, and are to be taken with food or a few minutes before a meal.

Brand names[edit]

  • Biltricide (Bayer) 600 mg Tablets (for human use)
  • Cesol (Merck) Tablets
  • Cestoved (Vedco) both tablets and injectable for veterinary use
  • Cysticide (Merck) Tablets
  • Distoside (Chandra Bhagat Pharma Pvt Ltd) 600mg 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
  • Profender (combination with emodepside) (Bayer) for veterinary use
  • Tape Worm Tabs (Trade Winds) for veterinary use
  • Zentozide (Berich (Thailand) Co)

References[edit]

  1. ^ Matthaiou DK, Panos G, Adamidi ES, Falagas ME (2008). "Albendazole versus Praziquantel in the Treatment of Neurocysticercosis: A Meta-analysis of Comparative Trials". In Carabin, Hélène. PLoS Negl Trop Dis 2 (3): e194. doi:10.1371/journal.pntd.0000194. PMC 2265431. PMID 18335068. 
  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. 
  3. ^ 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. PMID 15642971. 
  4. ^ a b The Carter Center. "Schistosomiasis Control Program". Retrieved 2008-07-17. 
  5. ^ 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. 
  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. PMID 16150452. 
  7. ^ "Treatment of fish parasites. 2. Effects of praziquantel, niclosamide, levamisole-HCl, and metrifonate on monogenea (Gyrodactylus aculeati, Diplozoon paradoxum)". 
  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 of Praziquantel". In Geary, Timothy G. PLoS Neglected Tropical Diseases 5 (9): e1260. doi:10.1371/journal.pntd.0001260. PMC 3176743. PMID 21949890.  edit
  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. PMID 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. PMID 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. PMID 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. 
  14. ^ 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. PMC 163896. PMID 9174180. 

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