Praziquantel Information Continued...

The 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, 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."[15]
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.[16]
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 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.[6]
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.
Society and culture[edit]
Brand names[edit]
Biltricide (Bayer) Tablets (for human use)[17]
Cesol (Merck) Tablets
Cestoved (Vedco) both tablets and injectable for veterinary use
Cysticide (Merck) Tablets
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[edit]
Praziquantel is on the World Health Organization's List of Essential Medicines, the most important medications needed in a basic health system.[1]
Praziquantel is not licensed for use in humans in the UK but it can be imported when necessary on a named patient basis.[18] It is available in the UK as a veterinary anthelmintic.
Praziquantel is FDA approved in the US for the treatment of schistosomiasis and liver fluke, although it is effective in other infections.[19]
References[edit]
^ Jump up to: a b "WHO Model List of EssentialMedicines" (PDF). World Health Organization. October 2013. Retrieved 22 April 2014.
Jump up ^ Matthaiou DK, Panos G, Adamidi ES, Falagas ME (2008). Carabin, Hélène, 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.
^ Jump up to: a b c Drontal Data Sheet; Drontal Cat & Cat XL Film-coated Tablets, Bayer plc (PDF), Newbury, England: Bayer plc, Animal Health Division, p. 2, retrieved 23 September 2015
^ Jump up to: a b 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.
Jump up ^ 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.
^ Jump up to: a b The Carter Center. "Schistosomiasis Control Program". Retrieved 2008-07-17.
Jump up ^ 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.
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Jump up ^ "Treatment of fish parasites. 2. Effects of praziquantel, niclosamide, levamisole-HCl, and metrifonate on monogenea (Gyrodactylus aculeati, Diplozoon paradoxum)".
Jump up ^ 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.
Jump up ^ 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.
Jump up ^ 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.
Jump up ^ 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.
Jump up ^ 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.
Jump up ^ http://bayer.naccvp.com/view_label.php
Jump up ^ 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.
Jump up ^ "BILTRICIDE- praziquantel tablet, film coated (NDC Code(s): 50419-747-01)". DailyMed. July 2015. Retrieved 2015-09-08.
Jump up ^ "Antihelmintics - Medicines for Worms; threadword, roundworm". Patient. Retrieved 2015-06-15.
Jump up ^ 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.