Difference between revisions of "Praziquantel"
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| − | {{Drugbox| Watchedfields = changed | + | {{Drugbox |
| + | | Watchedfields = changed | ||
| verifiedrevid = 312318203 | | verifiedrevid = 312318203 | ||
| − | + | | image=Praziquantel.svg | |
| − | |image=Praziquantel.svg | + | | image2=Praziquantel.gif |
| − | |image2=Praziquantel.gif | + | | IUPAC_name = (''RS'')-2-(Cyclohexanecarbonyl)-2,3,6,7-tetrahydro-1''H''-pyrazino[2,1-''a'']isoquinolin-4(11b''H'')-one |
| − | |IUPAC_name = (''RS'')-2-( | + | |
| CASNo_Ref = {{cascite}} | | CASNo_Ref = {{cascite}} | ||
| CAS_number=55268-74-1 | | CAS_number=55268-74-1 | ||
| Line 12: | Line 12: | ||
| PubChem=4891 | | PubChem=4891 | ||
| DrugBank=EXPT02728 | | DrugBank=EXPT02728 | ||
| − | + | | C=19 | H=24 | N=2 | O=2 | |
| molecular_weight = 312.411 | | molecular_weight = 312.411 | ||
| bioavailability = relatively small | | bioavailability = relatively small | ||
| Line 22: | Line 22: | ||
| routes_of_administration= oral | | routes_of_administration= oral | ||
}} | }} | ||
| − | |||
| − | 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. | + | '''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== | ==Uses== | ||
===Flukes/trematodes=== | ===Flukes/trematodes=== | ||
| − | + | Praziquantel is used against ''[[Schistosoma]]''.<ref name="pmid15642971">{{cite journal |author=Tchuenté LA, Shaw DJ, Polla L, Cioli D, Vercruysse J |title=Efficacy of praziquantel against Schistosoma haematobium infection in children |journal=Am. J. Trop. Med. Hyg. |volume=71 |issue=6 |pages=778–82 |year=2004 |month=December |pmid=15642971 |doi= |url=http://www.ajtmh.org/cgi/pmidlookup?view=long&pmid=15642971}}</ref> As of 2005, praziquantel is the primary treatment for human [[schistosomiasis]], for which it is usually effective in a single dose.<ref name="SCP">{{Cite web | author= The Carter Center| title="Schistosomiasis Control Program" | url=http://www.cartercenter.org/health/schistosomiasis/index.html |accessdate=2008-07-17}}</ref> | |
| − | + | Praziquantel is also used to treat [[liver fluke]]s such as ''[[Clonorchis sinensis]]'', <ref name="pmid17570980">{{cite journal |author=Shen C, Kim J, Lee JK, ''et al.'' |title=Collection of Clonorchis sinensis adult worms from infected humans after praziquantel treatment |journal=Korean J. Parasitol. |volume=45 |issue=2 |pages=149–52 |year=2007 |month=June |pmid=17570980 |pmc=2526309 |doi= 10.3347/kjp.2007.45.2.149|url=http://www.parasitol.or.kr/kjp/abstracts/2007_149.html}}</ref> but it is not effective against [[fascioliasis]].{{Fact|date=December 2008}} | |
| − | + | Praziquantel is also used to treat [[paragonimiasis]]. | |
| − | ===Tapeworms | + | ===Tapeworms and cestodes=== |
| − | + | Praziquantel is also used to treat [[tapeworm]]s and [[cestode]]s, including: | |
* [[Echinococcosis]] | * [[Echinococcosis]] | ||
| − | * [[Cysticercosis]] | + | * [[Cysticercosis]], though it has been judged less effective than [[albendazole]] in treatment of [[neurocysticercosis]].)<ref name="pmid18335068">{{cite journal |author=Matthaiou DK, Panos G, Adamidi ES, Falagas ME |title=Albendazole versus Praziquantel in the Treatment of Neurocysticercosis: A Meta-analysis of Comparative Trials |journal=PLoS Negl Trop Dis |volume=2 |issue=3 |pages=e194 |year=2008 |pmid=18335068 |pmc=2265431 |doi=10.1371/journal.pntd.0000194 |url=http://www.plosntds.org/article/info:doi/10.1371/journal.pntd.0000194}}</ref> |
| − | * [[intestine|Intestinal]] [[tapeworm]]s. In [[veterinary medicine]] it is widely used against [[tapeworm]]s, either alone | + | * [[intestine|Intestinal]] [[tapeworm]]s. In [[veterinary medicine]] it is widely used against [[tapeworm]]s, either alone or in combination with [[pyrantel pamoate]]. |
==History== | ==History== | ||
| Line 44: | Line 43: | ||
==Pharmacokinetics== | ==Pharmacokinetics== | ||
| − | Praziquantel is well (approximately 80%) | + | Praziquantel is well absorbed (approximately 80%) from the [[gastrointestinal tract]]. However, due to extensive [[First pass effect|first-pass metabolism]], only a relatively small amount enters systemic circulation. Praziquantel has a [[Blood serum|serum]] [[half-life]] of 0.8 to 1.5 hours in adults with normal renal and liver function. [[Metabolite]]s 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 [[Enzyme induction and inhibition|induce]] or [[Enzyme inhibitor|inhibit]] CYP3A4 such as [[phenytoin]], [[rifampin]], and [[azole antifungals#Imidazole_and_triazole_antifungals|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.<ref name="SCP"/> | 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.<ref name="SCP"/> | ||
==Mode of action== | ==Mode of action== | ||
| − | Although the mode of action is not exactly known at present, there is experimental evidence that | + | Although 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 | + | 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 [[purine]]s such as adenosine ''de novo''. |
| − | Bayer's Animal Health Division | + | 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.1 Following exposure to praziquantel, the tapeworm loses its ability to resist digestion by the mammalian host. Because of this, whole tapeworms, including the scolices, 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."<ref>[http://bayer.naccvp.com/view_label.php]</ref> |
==Side effects== | ==Side effects== | ||
| Line 66: | Line 65: | ||
===Antibiotics=== | ===Antibiotics=== | ||
| − | A study found that the antibiotic [[rifampicin]] decreases plasmatic concentrations of praziquantel.<ref>{{cite journal |author=Ridtitid W, Wongnawa M, Mahatthanatrakul W, Punyo J, Sunbhanich M |title=Rifampin markedly decreases plasma concentrations of praziquantel in healthy volunteers |journal=Clin. Pharmacol. Ther. |volume=72 |issue=5 |pages=505–13 |year=2002 |month=November |pmid=12426514 |doi=10 | + | A study found that the antibiotic [[rifampicin]] decreases plasmatic concentrations of praziquantel.<ref>{{cite journal |author=Ridtitid W, Wongnawa M, Mahatthanatrakul W, Punyo J, Sunbhanich M |title=Rifampin markedly decreases plasma concentrations of praziquantel in healthy volunteers |journal=Clin. Pharmacol. Ther. |volume=72 |issue=5 |pages=505–13 |year=2002 |month=November |pmid=12426514 |doi=10.1067/mcp.2002.129319}}</ref> |
===Antiepileptics=== | ===Antiepileptics=== | ||
| − | [[Carbamazepine]] and [[phenytoin]] are reported to reduce the bioavailability of praziquantel.<ref>{{cite journal |author=Quinn DI, Day RO |title=Drug interactions of clinical importance. An updated guide |journal=Drug Saf |volume=12 |issue=6 |pages=393–452 |year=1995 |month=June |pmid=8527014 }}</ref> | + | [[Carbamazepine]] and [[phenytoin]] are reported to reduce the bioavailability of praziquantel.<ref>{{cite journal |author=Quinn DI, Day RO |title=Drug interactions of clinical importance. An updated guide |journal=Drug Saf |volume=12 |issue=6 |pages=393–452 |year=1995 |month=June |pmid=8527014 |doi=10.2165/00002018-199512060-00005 }}</ref> |
===Antimalarials=== | ===Antimalarials=== | ||
| − | [[Chloroquine]] reduces the bioavailability of praziquantel.<ref>{{cite journal |author=Masimirembwa CM, Naik YS, Hasler JA |title=The effect of chloroquine on the pharmacokinetics and metabolism of praziquantel in rats and in humans |journal=Biopharm Drug Dispos |volume=15 |issue=1 |pages=33–43 |year=1994 |month=January |pmid=8161714 }}</ref> | + | [[Chloroquine]] reduces the bioavailability of praziquantel.<ref>{{cite journal |author=Masimirembwa CM, Naik YS, Hasler JA |title=The effect of chloroquine on the pharmacokinetics and metabolism of praziquantel in rats and in humans |journal=Biopharm Drug Dispos |volume=15 |issue=1 |pages=33–43 |year=1994 |month=January |pmid=8161714 |doi=10.1002/bdd.2510150103 }}</ref> |
===Antacids / histamine H<sub>2</sub>-antagonists=== | ===Antacids / histamine H<sub>2</sub>-antagonists=== | ||
| Line 81: | Line 80: | ||
==Dosage== | ==Dosage== | ||
| − | For schistosomiasis, the dose is 20 milligrams/kilogram by mouth every 4-6 hours for one day. | + | 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. |
| − | + | ||
| − | 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. | + | |
==Brand names== | ==Brand names== | ||
Revision as of 21:36, 10 September 2010
| File:Praziquantel.svg | |
| File:Praziquantel.gif | |
| Systematic (IUPAC) name | |
|---|---|
|
(RS)-2-(Cyclohexanecarbonyl)-2,3,6,7-tetrahydro-1H-pyrazino[2,1-a]isoquinolin-4(11bH)-one | |
| Clinical data | |
| Pregnancy category |
|
| Routes of administration | oral |
| Legal status | |
| Legal status |
|
| Pharmacokinetic data | |
| Bioavailability | relatively small |
| Metabolism | hepatic |
| Biological 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 (WHO) QP52AA01 |
| PubChem | CID 4891 |
| DrugBank | EXPT02728 |
| Chemical data | |
| Formula | C19H24N2O2 |
| Molar mass | 312.411[[Script error: No such module "String".]] |
| (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.
Contents
Uses
Flukes/trematodes
Praziquantel is used against Schistosoma.[1] As of 2005, praziquantel is the primary treatment for human schistosomiasis, for which it is usually effective in a single dose.[2]
Praziquantel is also used to treat liver flukes such as Clonorchis sinensis, [3] but it is not effective against fascioliasis.[citation needed]
Praziquantel is also used to treat paragonimiasis.
Tapeworms and cestodes
Praziquantel is also used to treat tapeworms and cestodes, including:
- Echinococcosis
- Cysticercosis, though it has been judged less effective than albendazole in treatment of neurocysticercosis.)[4]
- Intestinal tapeworms. In veterinary medicine it is widely used against tapeworms, either alone or in combination with pyrantel pamoate.
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. The World Health Organization includes it on its Model List of Essential Medicines.
Pharmacokinetics
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.[2]
Mode of action
Although 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.1 Following exposure to praziquantel, the tapeworm loses its ability to resist digestion by the mammalian host. Because of this, whole tapeworms, including the scolices, 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."[5]
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: 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 preexisting 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 Counts.
- Other locations/Body as a whole: Lower back pain, myalgia, arthralgia, fever, sweating, various cardiac arrhythmias, and hypotension.
Drug interactions
Antibiotics
A study found that the antibiotic rifampicin decreases plasmatic concentrations of praziquantel.[6]
Antiepileptics
Carbamazepine and phenytoin are reported to reduce the bioavailability of praziquantel.[7]
Antimalarials
Chloroquine reduces the bioavailability of praziquantel.[8]
Antacids / histamine H2-antagonists
At least 2 studies indicate the drug cimetidine heightens praziquantel bioavailability.[9][10]
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 one day. These dosages are for patients over 4 years old, and are to be taken with food.
Brand names
- Biltricide (Bayer) 600 mg Tablets (for human use)
- Cesol (Merck) Tablets
- Kaicide (Taiwan)
- Cysticide (Merck) Tablets
- Zentozide (Berich (Thailand) Co)
- Profender (combination with emodepside) (Bayer) for veterinary 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.
- Tape Worm Tabs (Trade Winds) for veterinary use
- Cestoved (Vedco) both tablets and injectable for veterinary use
- PraziPro (Hikari) for aquarium use
References
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ru:Празиквантел- ↑ Lua error in package.lua at line 80: module 'Module:Citation/CS1/Suggestions' not found.
- ↑ 2.0 2.1 The Carter Center. ""Schistosomiasis Control Program"". Retrieved 2008-07-17.
- ↑ Lua error in package.lua at line 80: module 'Module:Citation/CS1/Suggestions' not found.
- ↑ Matthaiou DK, Panos G, Adamidi ES, Falagas ME (2008). "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 Freely accessible. PMID 18335068.
- ↑ [2]
- ↑ Lua error in package.lua at line 80: module 'Module:Citation/CS1/Suggestions' not found.
- ↑ Lua error in package.lua at line 80: module 'Module:Citation/CS1/Suggestions' not found.
- ↑ Lua error in package.lua at line 80: module 'Module:Citation/CS1/Suggestions' not found.
- ↑ Lua error in package.lua at line 80: module 'Module:Citation/CS1/Suggestions' not found.
- ↑ Lua error in package.lua at line 80: module 'Module:Citation/CS1/Suggestions' not found.
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