Praziquantel

 



 

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 136-140C 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 Egypt under license from Shin Poong. This was soon followed by other producers in various countries. (Source).

 

 

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

  Unit Price

  IDA

500 Tab-cap    (Tablets)

 

$ 40.28

0.0806/Tab-cap

  JMS

500 Tab-cap    (Tablets)

 

$ 48.85

0.0977/Tab-cap

  MISSION

500 Tab-cap    (Tablets)

 

$ 55.01

0.1100/Tab-cap

  MEDS

100 Tab-cap    (Tablets)

 

$ 11.29

0.1129/Tab-cap

  DURBIN

1000 Tab-cap    (Tablets)

 

$ 117.71

0.1177/Tab-cap

  ACTION

250 Tab-cap    (Tablets)

 

$ 32.40

0.1296/Tab-cap

  ORBI

100 Tab-cap    (Tablets)

 

$ 16.10

0.1610/Tab-cap

 

Agency Prices

 

Source

Package

 

Package Price

  Unit Price

 

   YEMEN

500 Tab-cap    (Tablets)

 

$ 46.39

0.0928 /Tab-cap

 

   SENEGAL

1 Tab-cap    (Tablet)

 

$ 0.09

0.0948 /Tab-cap

 

   MEMS

100 Tab-cap    (Tablets)

 

$ 11.70

0.1170 /Tab-cap

 

   NAMIBIA

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 (Pharco, Egypt), and Prazitel (Cosmos, Kenya). (Source).

 

 

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 Egypt and Senegal. However, apparent resistance could be the result of the odd efficacy of praziquantel and high rates of reinfection. An article from 2000 on the CDC website predicted the emergence of a resistant strain in Kenya was 10 year away. Resistant strains are either not yet highly resistant or are not yet widely prevalent. Any widespread resistant strain will most likely arise in the highly endemic areas of Africa.