Praziquantel
Encyclopedia
Praziquantel 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.
. As of 2005, praziquantel is the primary treatment for human schistosomiasis
, for which it is usually effective in a single dose.
Praziquantel is also used to treat liver fluke
s such as Clonorchis sinensis
, and against fascioliasis
.
Praziquantel is also used to treat paragonimiasis
.
in Germany (Elberfeld and Darmstadt) in the mid 1970s. The World Health Organization
includes it on its Model List of Essential Medicines
.
. 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. 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 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.
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 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, 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."
decreases plasma concentrations of praziquantel.
and phenytoin
are reported to reduce the bioavailability of praziquantel.
heightens praziquantel bioavailability.
Anthelmintic
Anthelmintics or antihelminthics are drugs that expel parasitic worms from the body, by either stunning or killing them. They may also be called vermifuges or vermicides .-Pharmaceutical classes:...
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.
Flukes/trematodes
Praziquantel is used against SchistosomaSchistosoma
A genus of trematodes, Schistosoma, commonly known as blood-flukes and bilharzia, includes flatworms which are responsible for a highly significant parasitic infection of humans by causing the disease schistosomiasis, and are considered by the World Health Organization as the second most...
. As of 2005, praziquantel is the primary treatment for human schistosomiasis
Schistosomiasis
Schistosomiasis is a parasitic disease caused by several species of trematodes , a parasitic worm of the genus Schistosoma. Snails often act as an intermediary agent for the infectious diseases until a new human host is found...
, for which it is usually effective in a single dose.
Praziquantel is also used to treat liver fluke
Liver fluke
Liver flukes are a polyphyletic group of trematodes .Adults of liver flukes are localized in the liver of various mammals, including humans. These flatworms can occur in bile ducts, gallbladder, and liver parenchyma. They feed on blood...
s such as Clonorchis sinensis
Clonorchis sinensis
Clonorchis sinensis, the Chinese liver fluke, is a human liver fluke in the class Trematoda, Phylum Platyhelminthes. This parasite lives in the liver of humans, and is found mainly in the common bile duct and gall bladder, feeding on bile...
, and against fascioliasis
Fascioliasis
Fasciolosis also known as Fascioliasis, Fasciolasis, distomatosis and liver rot, is an important helminth disease caused by two trematodes Fasciola hepatica and Fasciola gigantica. This disease belongs to the plant-borne trematode zoonoses. In Europe, the Americas and Oceania only F...
.
Praziquantel is also used to treat paragonimiasis
Paragonimiasis
Paragonimiasis is a food-borne parasitic infection caused by the lung fluke, most commonly Paragonimus westermani. It infects an estimated 22 million people worldwide. It is particularly common in East Asia. More than 30 species of trematodes of the genus Paragonimus have been reported which...
.
Tapeworms/cestodes
Praziquantel is also used to treat cestode (tapeworm) infections, including:- EchinococcosisEchinococcosisEchinococcosis, which is often referred to as hydatid disease or echinococcal disease, is a parasitic disease that affects both humans and other mammals, such as sheep, dogs, rodents and horses. There are three different forms of echinococcosis found in humans, each of which is caused by the larval...
- CysticercosisCysticercosisCysticercosis refers to tissue infection after exposure to eggs of Taenia solium, the pork tapeworm. The disease is spread via the fecal-oral route through contaminated food and water, and is primarily a food borne disease. After ingestion the eggs pass through the lumen of the intestine into the...
, though it has been judged less effective than albendazoleAlbendazoleAlbendazole, marketed as Albenza, Eskazole, Zentel and Andazol, is a member of the benzimidazole compounds used as a drug indicated for the treatment of a variety of worm infestations. Although this use is widespread in the United States, the U.S. Food and Drug Administration has not approved...
in treatment of neurocysticercosis. - IntestinalIntestineIn human anatomy, the intestine is the segment of the alimentary canal extending from the pyloric sphincter of the stomach to the anus and, in humans and other mammals, consists of two segments, the small intestine and the large intestine...
tapeworms. In veterinary medicineVeterinary medicineVeterinary Medicine is the branch of science that deals with the prevention, diagnosis and treatment of disease, disorder and injury in non-human animals...
it is widely used against tapeworms, either alone or in combination with pyrantel pamoatePyrantel pamoatePyrantel pamoate or Pyrantel Embonate , is used as a deworming agent in the treatment of hookworms and roundworms in domesticated animals such as horses, cattle, sheep, pigs, cats, dogs, and many other species. It is a combination of pyrantel and pamoic acid...
.
History
Praziquantel was developed in the laboratories for parasitological research of Bayer AG and Merck KGaAMerck KGaA
Merck KGaA is a German chemical and pharmaceutical company. Merck, also known as “German Merck” and “Merck Darmstadt”, was founded in Darmstadt, Germany, in 1668, making it the world's oldest operating chemical and pharmaceutical company. The company was privately owned until going public in 1995...
in Germany (Elberfeld and Darmstadt) in the mid 1970s. The World Health Organization
World Health Organization
The World Health Organization is a specialized agency of the United Nations that acts as a coordinating authority on international public health. Established on 7 April 1948, with headquarters in Geneva, Switzerland, the agency inherited the mandate and resources of its predecessor, the Health...
includes it on its Model List of Essential Medicines
Essential medicines
Essential medicines, as defined by the World Health Organization are "those drugs that satisfy the health care needs of the majority of the population; they should therefore be available at all times in adequate amounts and in appropriate dosage forms, at a price the community can afford."The WHO...
.
Pharmacokinetics
Praziquantel is well absorbed (approximately 80%) from the gastrointestinal tractGastrointestinal tract
The human gastrointestinal tract refers to the stomach and intestine, and sometimes to all the structures from the mouth to the anus. ....
. However, due to extensive first-pass metabolism
First pass effect
The first-pass effect is a phenomenon of drug metabolism whereby the concentration of a drug is greatly reduced before it reaches the systemic circulation. It is the fraction of lost drug during the process of absorption which is generally related to the liver and gut wall...
, only a relatively small amount enters systemic circulation. Praziquantel has a serum
Blood serum
In blood, the serum is the component that is neither a blood cell nor a clotting factor; it is the blood plasma with the fibrinogens removed...
half-life
Half-life
Half-life, abbreviated t½, is the period of time it takes for the amount of a substance undergoing decay to decrease by half. The name was originally used to describe a characteristic of unstable atoms , but it may apply to any quantity which follows a set-rate decay.The original term, dating to...
of 0.8 to 1.5 hours in adults with normal renal and liver function. Metabolite
Metabolite
Metabolites are the intermediates and products of metabolism. The term metabolite is usually restricted to small molecules. A primary metabolite is directly involved in normal growth, development, and reproduction. Alcohol is an example of a primary metabolite produced in large-scale by industrial...
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
CYP3A4
Cytochrome P450 3A4 , a member of the cytochrome P450 mixed-function oxidase system, is one of the most important enzymes involved in the metabolism of xenobiotics in the body. CYP3A4 is involved in the oxidation of the largest range of substrates of all the CYPs. As a result, CYP3A4 is present in...
. Agents that induce
Enzyme induction and inhibition
Enzyme induction is a process in which a molecule induces the expression of an enzyme.Enzyme inhibition can refer to* the inhibition of the expression of the enzyme by another molecule...
or inhibit
Enzyme inhibitor
An enzyme inhibitor is a molecule that binds to enzymes and decreases their activity. Since blocking an enzyme's activity can kill a pathogen or correct a metabolic imbalance, many drugs are enzyme inhibitors. They are also used as herbicides and pesticides...
CYP3A4 such as phenytoin
Phenytoin
Phenytoin sodium is a commonly used antiepileptic. Phenytoin acts to suppress the abnormal brain activity seen in seizure by reducing electrical conductance among brain cells by stabilizing the inactive state of voltage-gated sodium channels...
, 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.
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
Taenia
Taenia can refer to:* Taenia of Doric columnsIn medicine and anatomy* Taenia coli of the large intestine* Taenia thalami of the mammal brain* Taenia of fourth ventricle of the mammal brain...
and the echinococcus
Echinococcus
The genus Echinococcus includes six species of cyclophyllid tapeworms to date, of the family Taeniidae. Infection with Echinococcus results in hydatid disease, also known as echinococcosis....
(other praziquantel sensitive parasites), is unable to synthesize purine
Purine
A purine is a heterocyclic aromatic organic compound, consisting of a pyrimidine ring fused to an imidazole ring. Purines, including substituted purines and their tautomers, are the most widely distributed kind of nitrogen-containing heterocycle in nature....
s 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, 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."
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 dizzinessDizzinessDizziness refers to an impairment in spatial perception and stability. The term is somewhat imprecise. It can be used to mean vertigo, presyncope, disequilibrium, or a non-specific feeling such as giddiness or foolishness....
, headacheHeadacheA headache or cephalalgia is pain anywhere in the region of the head or neck. It can be a symptom of a number of different conditions of the head and neck. The brain tissue itself is not sensitive to pain because it lacks pain receptors. Rather, the pain is caused by disturbance of the...
, and malaise. Drowsiness, somnolenceSomnolenceSomnolence is a state of near-sleep, a strong desire for sleep, or sleeping for unusually long periods . It has two distinct meanings, referring both to the usual state preceding falling asleep, and the chronic condition referring to being in that state independent of a circadian rhythm...
, fatigueFatigue (physical)Fatigue is a state of awareness describing a range of afflictions, usually associated with physical and/or mental weakness, though varying from a general state of lethargy to a specific work-induced burning sensation within one's muscles...
, and vertigoVertigo (medical)Vertigo is a type of dizziness, where there is a feeling of motion when one is stationary. The symptoms are due to a dysfunction of the vestibular system in the inner ear...
have also been seen. Almost all patients with cerebral cysticercosisCysticercosisCysticercosis refers to tissue infection after exposure to eggs of Taenia solium, the pork tapeworm. The disease is spread via the fecal-oral route through contaminated food and water, and is primarily a food borne disease. After ingestion the eggs pass through the lumen of the intestine into the...
experience CNS side effects related to the cell-death of the parasites (headache, worsening of pre-existing neurological problems, seizures, arachnoiditisArachnoiditisArachnoiditis is a neuropathic disease caused by the inflammation of the arachnoid, one of the membranes that surround and protect the nerves of the central nervous system, including the brain and spinal cord...
, and meningismMeningismMeningism is the triad of nuchal rigidity , photophobia and headache. It is a sign of irritation of the meninges, such as seen in meningitis, subarachnoid hemorrhages and various other diseases...
). These side effects may be life-threatening and can be reduced by coadministration of corticosteroidCorticosteroidCorticosteroids are a class of steroid hormones that are produced in the adrenal cortex. Corticosteroids are involved in a wide range of physiologic systems such as stress response, immune response and regulation of inflammation, carbohydrate metabolism, protein catabolism, blood electrolyte...
s. It is strongly recommended that all patients with cerebral cysticercosisCysticercosisCysticercosis refers to tissue infection after exposure to eggs of Taenia solium, the pork tapeworm. The disease is spread via the fecal-oral route through contaminated food and water, and is primarily a food borne disease. After ingestion the eggs pass through the lumen of the intestine into the...
are hospitalized during treatment. - GI Tract: Approximately 90% of all patients have abdominal pain or cramps with or without nausea and vomiting. DiarrheaDiarrheaDiarrhea , also spelled diarrhoea, is the condition of having three or more loose or liquid bowel movements per day. It is a common cause of death in developing countries and the second most common cause of infant deaths worldwide. The loss of fluids through diarrhea can cause dehydration and...
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 (ASTAspartate transaminaseAspartate transaminase , also called aspartate aminotransferase or serum glutamic oxaloacetic transaminase , is a pyridoxal phosphate -dependent transaminase enzyme . AST catalyzes the reversible transfer of an α-amino group between aspartate and glutamate and, as such, is an important enzyme in...
and ALTAlanine transaminaseAlanine transaminase or ALT is a transaminase enzyme . It is also called serum glutamic pyruvic transaminase or alanine aminotransferase ....
) are noted frequently (up to 27%). No case of symptomatic liver damage has ever been seen so far. - Sensitivity reactions: UrticariaUrticariaUrticaria is a kind of skin rash notable for pale red, raised, itchy bumps. Hives is frequently caused by allergic reactions; however, there are many non-allergic causes...
, rashRashA rash is a change of the skin which affects its color, appearance or texture. A rash may be localized in one part of the body, or affect all the skin. Rashes may cause the skin to change color, itch, become warm, bumpy, chapped, dry, cracked or blistered, swell and may be painful. The causes, and...
, 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 hypotensionHypotensionIn physiology and medicine, hypotension is abnormally low blood pressure, especially in the arteries of the systemic circulation. It is best understood as a physiologic state, rather than a disease. It is often associated with shock, though not necessarily indicative of it. Hypotension is the...
Antibiotics
A study found that the antibiotic rifampicinRifampicin
Rifampicin or rifampin is a bactericidal antibiotic drug of the rifamycin group. It is a semisynthetic compound derived from Amycolatopsis rifamycinica ...
decreases plasma concentrations of praziquantel.
Antiepileptics
CarbamazepineCarbamazepine
Carbamazepine is an anticonvulsant and mood-stabilizing drug used primarily in the treatment of epilepsy and bipolar disorder, as well as trigeminal neuralgia...
and phenytoin
Phenytoin
Phenytoin sodium is a commonly used antiepileptic. Phenytoin acts to suppress the abnormal brain activity seen in seizure by reducing electrical conductance among brain cells by stabilizing the inactive state of voltage-gated sodium channels...
are reported to reduce the bioavailability of praziquantel.
Antacids / histamine H2-antagonists
At least 2 studies indicate the drug cimetidineCimetidine
Cimetidine INN is a histamine H2-receptor antagonist that inhibits the production of acid in the stomach. It is largely used in the treatment of heartburn and peptic ulcers. It is marketed by GlaxoSmithKline under the trade name Tagamet...
heightens praziquantel bioavailability.
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 or a few minutes before a meal.Brand names
- Biltricide (Bayer) 600 mg Tablets (for human use)
- Cesol (Merck) Tablets
- Cestoved (Vedco) both tablets and injectable for veterinary use
- Cysticide (Merck) Tablets
- Droncit (Bayer) for veterinary use
- Drontal (combination with pyrantel pamoatePyrantel pamoatePyrantel pamoate or Pyrantel Embonate , is used as a deworming agent in the treatment of hookworms and roundworms in domesticated animals such as horses, cattle, sheep, pigs, cats, dogs, and many other species. It is a combination of pyrantel and pamoic acid...
) (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.
- Kaicide (Taiwan)
- Milbemax (combination with milbemycin oximeMilbemycin oximeMilbemycin oxime is a veterinary drug from the group of milbemycins, used as a broad spectrum antiparasitic. It is active against worms , insects and mites ....
) (NovartisNovartisNovartis International AG is a multinational pharmaceutical company based in Basel, Switzerland, ranking number three in sales among the world-wide industry...
) for vetinerary use - Popantel (Jurox)
- PraziPro (Hikari) for aquarium use
- Profender (combination with emodepsideEmodepsideEmodepside is an anthelmintic drug that is effective against a number of gastrointestinal nematodes, is licensed for use in cats and belongs to the class of drugs known as the octadepsipeptides, a relatively new class of anthelmintic , which are suspected to achieve their anti-parasitic effect by a...
) (Bayer) for veterinary use - Tape Worm Tabs (Trade Winds) for veterinary use
- Zentozide (Berich (Thailand) Co)