Introduction
Praziquantel is a systemic anthelmintic used primarily to treat worm infections. It is currently the most effective drug for the treatment of schistosomiasis. Originally developed for veterinary applications, for humans it is a low cost, effective drug with mild side effects. It is most often taken orally in tablet form. The drug name's etymology is p(y)razi(ne), one of its components (from German Pyrazin, blend of Pyridin, pyridine and Azin, azine) + qu(inoline) + ant(h)el(mintic) (American Heritage Dictionary).
Structure
Praziquantel is
2-(cyclohexylcarbonyl)-1,2,3,6,7,11b-hexahydro-4H-pyrazino[2,1-a]isoquinoline-4-one.
It is a white to nearly white crystalline powder of bitter taste, melting
at 136-140°C with decomposition. It is stable under normal conditions and
it is practically insoluble in water, sparingly soluble in ethanol and
soluble in organic solvents like chloroform and dimethylsulfoxide. Praziquantel possesses an asymmetric
center in position 11b (asterisk). The commercial preparation is a racemate
composed of equal parts of "levo" R(-) and "dextro"
S(+) isomers. Only the (-)-enantiomer is endowed with antischistosomal
activity. http://parasitology.informatik.uni-wuerzburg.de
History
The anticestode and antitrematode
activities in animals of praziquantel, and the first studies on human
volunteers were reported in the late 1970's.
In close cooperation with the World Health Organization, the first
clinical trials were carried out in areas endemic for schistosomiasis. All of these trials, as well as numerous
subsequent ones, were extremely successful and clearly identified praziquantel
as the drug of choice for the treatment of schistosomiasis. In 1983, the Korean company, Shin Poong,
developed a new method for the synthesis of praziquantel and obtained a process
patent for its product. This started a
market competition that rapidly resulted in conspicuous price reductions. In 1987, EIPICO started producing
praziquantel in
Mechanism of Action
Praziquantel works by causing
severe spasms and paralysis of the worms' muscles. This paralysis is accompanied - and probably
caused - by a rapid Ca 2+ influx inside the schistosome. Morphological alterations are another early
effect of praziquantel. These
morphological alterations are accompanied by an
increased exposure of schistosome antigens at the parasite surface. The worms are then either completely
destroyed in the intestine or passed in the stool. An interesting quirk of praziquantel is that
it is relatively ineffective against juvenile schistosomes. While initially effective, effectiveness
against schistosomes decreases until it reaches a minimum at 3-4 weeks. Effectiveness then increases again until it
is once again fully effective at 6-7 weeks.
Indications (other diseases)
Praziquantel is used as a treatment for all varieties of Schistosome. In addition it is used to treat human and animal cestodes and trematodes. Common human cestodes, or tapeworms, include Taenia solium and Diphyllobothrium latum. Common human trematodes, or flukes, are Clonorchis sinensis and Opisthorchis viverrini.
Follow the links to reach the CDC information on each parasite and the disease it causes.
The CDC's Division of Parasitic Diseases main page is at http://www.dpd.cdc.gov/DPDx/
Dosage
Animal Tapeworm
- Cats and kittens 6+ weeks of age. Tablets normally contain 23 mg.
4 lbs
and under give 1/2 tablet;
5-11 lbs give 1 tablet;
over 11 lbs give 1.5 tablets.
- Dog and puppies 4+ weeks old. Tablets normally contain 34 mg.
5 lbs and under give 1/2 tablet;
6-10 lbs give 1 tablet;
11-15 lbs give 1.5 tablets;
16-30 lbs give 2 tablets;
31-45 lbs give 3 tablets;
46-60 lbs give 4 tablets;
over 60 lbs give 5 tablets maximum.
All following dosages are for adults and children 4 or older.
Schistosomiasis
- 40-60 mg/kg as a single dose.
OR
- 3 doses of 20 mg/kg on one day at intervals of 4-6 hours.
Trematodes (clonorchiasis and opisthorchiasis)
- 3 doses of 25 mg/kg for 3 days.
Cestodes
- single low dose.
Neurocysticeriasis
- 50 mg/kg/day for 15 days.
Drug Interactions
|
Praziquantel |
Albendazole |
Increased plasma concentration of active metabolite of albendazole |
|
Praziquantel |
Carbamazepine |
Plasma-praziquantel concentration reduced |
|
Praziquantel |
Chloroquine |
Plasma-praziquantel concentration possibly reduced |
|
Praziquantel |
Dexamethasone |
Plasma-praziquantel concentration reduced |
|
Praziquantel |
Phenytoin |
Plasma-praziquantel concentration reduced |
Source: WHO Essential Medicines Library (Search for praziquantel).
Cost
Each tablet is 600 mg
Supplier Prices
|
Source |
Package |
|
Package
Price |
|
|
500
Tab-cap (Tablets) |
|
$ 40.28 |
0.0806/Tab-cap
|
|
|
500
Tab-cap (Tablets) |
|
$ 48.85 |
0.0977/Tab-cap
|
|
|
500
Tab-cap (Tablets) |
|
$ 55.01 |
0.1100/Tab-cap
|
|
|
100
Tab-cap (Tablets) |
|
$ 11.29 |
0.1129/Tab-cap
|
|
|
1000
Tab-cap (Tablets) |
|
$ 117.71 |
0.1177/Tab-cap
|
|
|
250
Tab-cap (Tablets) |
|
$ 32.40 |
0.1296/Tab-cap
|
|
|
100
Tab-cap (Tablets) |
|
$ 16.10 |
0.1610/Tab-cap
|
Agency Prices
|
Source |
Package |
|
Package
Price |
|
|
|
500
Tab-cap (Tablets) |
|
$ 46.39 |
0.0928
/Tab-cap |
|
|
|
1 Tab-cap
(Tablet) |
|
$ 0.09 |
0.0948
/Tab-cap |
|
|
|
100
Tab-cap (Tablets) |
|
$ 11.70 |
0.1170
/Tab-cap |
|
|
|
100
Tab-cap (Tablets) |
|
$ 18.69 |
0.1869
/Tab-cap |
|
figures from ERC: International Drug Price Indicator Guide (2004)
(check http://erc.msh.org for more up-to-date pricing)
Manufacturers
Praziquantel was initially (and
still is) marketed by Bayer under the name Biltricide for human use and under
the name Droncit for veterinary use. A number of other brands are now available
with various names in different countries, such as Distocide (Shin Poong,
EIPICO), Bilharzid (
Side effects
Common side effects include abdominal discomfort, nausea, vomiting, malaise, headache, dizziness, drowsiness, and rectal bleeding. Rarer side effects include hypersensitivity reactions, such as fever, pruritus, and eosinophilia (may be due to dead and dying parasites) (WHO EMLib).
Remember that individual reactions can occur and contact your doctor if you are experiencing a side effect not listed here.
Resistance
Resistant
strains have been indicated to exist in