praziquantel

Praziquantel

Systematic (IUPAC) name
(RS)-2-(Cyclohexylcarbonyl) -1,2,3,6,7,11b-hexahydro-4H-pyrazino (2,1-alpha) isoquinolin-4-one
Identifiers
CAS number	55268-74-1
ATC code	P02BA01 QP52AA01
PubChem	4891
DrugBank	EXPT02728
Chemical data
Formula	C19H24N2O2
Mol. mass	312.411
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
Therapeutic considerations
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
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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

Flukes/trematodes

It 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]

It is used to treat liver flukes (such as Clonorchis sinensis)^[3] except for fascioliasis.^{[citation needed]}

It is also used to treat paragonimiasis.

Tapeworms/cestodes

It is also used to treat:

• 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 under the trade name Droncit, or in combination with pyrantel pamoate under the trade name Drontal.

History

Praziquantel was developed in the laboratories for parasitological research of Bayer AG in Germany (Elberfeld) in the mid 1970s. The World Health Organization includes it on its Model List of Essential Medicines.

Pharmacokinetics

Praziquantel is well (approximately 80%) absorbed from the gastrointestinal tract. Due to extensive first-pass metabolization only relatively small amounts enter systemic circulation. Praziquantel has a serum halflife of 0.8 to 1.5 hours (metabolites 4 to 5 hours) in adults with normal renal and liver function. In patients with significantly impaired liver function (Child Pugh classes B and C) the serum halflife is increased to 3 to 8 hours. Praziquantel and its metabolites are mainly excreted in the urine, and within 24 hours after a single oral dose, 70 to 80% are found in urine, but less than 0.1% are found as the unchanged drug. Praziquantel is metabolized through the cytochrome P450 pathway 3A4. Agents that induce or inhibit Cyp450 3A4 (ie phenytoin, rifampin, azole antifungals) will have an effect 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 parasite cells (certain schistosomes) for 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 — focal disintegrations and disturbances of oviposition (laying of eggs) — are seen in other types of sensitive parasites.

Another hypothesis on 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 de novo.

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.^[5]

Antiepileptics

Carbamazepine and phenytoin are reported to reduce the bioavailability of praziquantel.^[6]

Antimalarials

Chloroquine reduces the bioavailability of praziquantel.^[7]

Antacids / histamine H₂-antagonists

At least 2 studies indicate the drug Cimetidine heightens praziquantel bioavailability.^[8][9]

Dosage

According to special dosing schedules for each different indication. Sometimes one single dose or a one-day treatment with divided doses may be sufficient.

Brand names

• Biltricide (Bayer) 600 mg Tablets (for human use)
• Cesol (Merck) Tablets
• 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