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Annals of Internal Medicine Feb 1989To identify advances in knowledge of the pharmacokinetics, mechanism of action, clinical use, and side effects of the antihelminthic drug praziquantel in the 5 years... (Review)
Review
PURPOSE
To identify advances in knowledge of the pharmacokinetics, mechanism of action, clinical use, and side effects of the antihelminthic drug praziquantel in the 5 years since its introduction in the United States.
DATA IDENTIFICATION
Studies reported from 1983 to July 1988 were identified by computer searches of MEDLINE and TOXLINE, and review of textbooks and review articles.
STUDY SELECTION
Of 57 articles originally identified, 39 were selected by two readers.
DATA EXTRACTION
Study quality and significance were independently assessed by each reader.
RESULTS OF DATA ANALYSIS
The pharmacokinetics and clinical efficacy of praziquantel have been well documented. Yet, despite extensive in vivo and in vitro laboratory studies, the drug's mechanism of action in killing parasites is unknown. Although the efficacy of praziquantel was first established for treating schistosomiasis, in the last 5 years its clinical use has been expanded to the treatment of intestinal, tissue, and lung flukes, and intestinal and tissue cestode infections, including neurocysticercosis. The introduction of praziquantel was a significant advance in antihelminthic therapy, in that it was effective therapy for several parasites that had been previously considered untreatable. Availability of a safe, effective broad-spectrum oral antihelminthic agent consolidated the central role of chemotherapy in population-based control of many trematode and cestode parasites. Randomized trials have shown, however, that older, cheaper agents may be more cost-effective in controlling Schistosoma mansoni and Schistosoma haematobium in some endemic areas.
CONCLUSIONS
Although praziquantel is the treatment of choice for most human trematode and cestode infections, cost factors have limited its use in developing countries.
Topics: Animals; Brain Diseases; Costs and Cost Analysis; Cysticercosis; Echinococcosis; Humans; Praziquantel; Schistosoma; Schistosomiasis; Time Factors; United States
PubMed: 2643915
DOI: 10.7326/0003-4819-110-4-290 -
Acta Tropica 2005Chemotherapy is widely acknowledged as the most important, rapid and cost-effective method of reducing morbidity due to schistosome infections. The discovery of... (Review)
Review
Chemotherapy is widely acknowledged as the most important, rapid and cost-effective method of reducing morbidity due to schistosome infections. The discovery of praziquantel in the 1970s has been a breakthrough for treatment of patients infected with schistosomes, including Schistosoma japonicum in China, and entire communities at risk of schistosomiasis. Praziquantel is usually administered in a single oral dose and has no or only mild and transient side effects. The drug is highly efficacious against S. japonicum, both in patients with acute and chronic stages of the infection, among subjects with extensive hepatosplenic involvement, and in patients with other complicated diseases. The cost of praziquantel has been reduced significantly over the past years. Hence, praziquantel has become the backbone of the national schistosomiasis control programme in China and in other countries where the disease remains endemic, most notably in sub-Saharan Africa. Chemotherapy with praziquantel also plays a role in transmission control of schistosomiasis, although transmission interruption cannot be reached by chemotherapy alone. Here, I review 30 years' of experiences gained with the use of praziquantel for clinical treatment and larger-scale control of schistosomiasis japonica in China.
Topics: Animals; Cattle; China; Drug Administration Schedule; Humans; Praziquantel; Schistosomiasis japonica; Schistosomicides
PubMed: 16125657
DOI: 10.1016/j.actatropica.2005.07.011 -
Science Translational Medicine Dec 2021Praziquantel (PZQ) is an essential medicine for treating parasitic flatworm infections such as schistosomiasis, which afflicts over 250 million people. However, PZQ is...
Praziquantel (PZQ) is an essential medicine for treating parasitic flatworm infections such as schistosomiasis, which afflicts over 250 million people. However, PZQ is not universally effective, lacking activity against liver flukes of the genus. The reason for this insensitivity is unclear, as the mechanism of PZQ action is unknown. Here, we use ligand- and target-based methods to demonstrate that PZQ activates a transient receptor potential melastatin ion channel (TRPM) in schistosomes by engaging a hydrophobic ligand binding pocket within the voltage sensor–like domain of the channel to cause calcium entry and worm paralysis. PZQ activates TRPM homologs in other PZQ-sensitive flukes, but not . However, a single amino acid change in the TRPM binding pocket, to mimic schistosome TRPM, confers PZQ sensitivity. After decades of clinical use, the molecular basis of PZQ action at a druggable TRP channel is resolved.
Topics: Animals; Anthelmintics; Humans; Ion Channels; Platyhelminths; Praziquantel; Schistosoma
PubMed: 34936384
DOI: 10.1126/scitranslmed.abj5832 -
PLoS Neglected Tropical Diseases Sep 2011Praziquantel remains the drug of choice for the worldwide treatment and control of schistosomiasis. The drug is synthesized and administered as a racemate. Use of the...
BACKGROUND
Praziquantel remains the drug of choice for the worldwide treatment and control of schistosomiasis. The drug is synthesized and administered as a racemate. Use of the pure active enantiomer would be desirable since the inactive enantiomer is associated with side effects and is responsible for the extremely bitter taste of the pill.
METHODOLOGY/PRINCIPAL FINDINGS
We have identified two resolution approaches toward the production of praziquantel as a single enantiomer. One approach starts with commercially available praziquantel and involves a hydrolysis to an intermediate amine, which is resolved with a derivative of tartaric acid. This method was discovered through an open collaboration on the internet. The second method, identified by a contract research organisation, employs a different intermediate that may be resolved with tartaric acid itself.
CONCLUSIONS/SIGNIFICANCE
Both resolution procedures identified show promise for the large-scale, economically viable production of praziquantel as a single enantiomer for a low price. Additionally, they may be employed by laboratories for the production of smaller amounts of enantiopure drug for research purposes that should be useful in, for example, elucidation of the drug's mechanism of action.
Topics: Anthelmintics; Chemistry, Pharmaceutical; Humans; International Cooperation; Praziquantel; Schistosomiasis; Stereoisomerism; Technology, Pharmaceutical
PubMed: 21949890
DOI: 10.1371/journal.pntd.0001260 -
Advances in Internal Medicine 1987
Review
Topics: Animals; Cestode Infections; Helminthiasis; Humans; Kinetics; Praziquantel; Schistosomiasis; Trematode Infections
PubMed: 3548250
DOI: No ID Found -
Arzneimittel-Forschung 19812-Cyclohexylcarbonyl-1,2,3,6,7,11b-hexahydro-4H-pyrazino[2,1-a]isoquinolin-4-one (praziquantel, EMBAY 8440, Biltricide) is broadly effective in mice, Syrian hamsters and... (Review)
Review
2-Cyclohexylcarbonyl-1,2,3,6,7,11b-hexahydro-4H-pyrazino[2,1-a]isoquinolin-4-one (praziquantel, EMBAY 8440, Biltricide) is broadly effective in mice, Syrian hamsters and Mastomys natalensis experimentally infected with Schistosoma mansoni, S. haematobium, S. japonicum, S. intercalatum, and S. mattheei. In vitro it is equally effective against all developmental stages of S. mansoni whilst in vivo it is especially effective against young schistosomules and mature worms. 14C-Praziquantel is rapidly taken up by S. mansoni and not transformed metabolically. In the mammal, however, metabolism of praziquantel is rapid and 80% of the orally administered dose is excreted in the urine within 24 h. Clinico-chemical and haematological studies have shown that praziquantel is well tolerated by mice heavily infected with S. mansoni. Praziquantel induces a rapid contraction of the schistosomes by a specific effect on the permeability of the cell membrane. In vivo it induces a rapid liver shift of the schistosomes. Praziquantel further results in a vacuolization and disintegration of the schistosome tegument.
Topics: Animals; Humans; Isoquinolines; Praziquantel; Schistosoma; Schistosoma mansoni; Schistosomiasis; Species Specificity
PubMed: 7016122
DOI: No ID Found -
Australian Veterinary Journal Feb 1998
Topics: Animals; Antiplatyhelmintic Agents; Praziquantel; Trematode Infections; Turtles
PubMed: 9578780
DOI: 10.1111/j.1751-0813.1998.tb14538.x -
Neurology Jun 1988
Topics: Adult; Aged; Central Nervous System Diseases; Cysticercosis; Dexamethasone; Female; Humans; Male; Middle Aged; Nervous System Diseases; Praziquantel
PubMed: 3368087
DOI: 10.1212/wnl.38.6.997-d -
Acta Tropica Dec 1990Early experimental studies suggested that doses of 1 to 5 mg of praziquantel (PZQ) per kg are effective against several intestinal cestodiases. The usually recommended... (Review)
Review
Early experimental studies suggested that doses of 1 to 5 mg of praziquantel (PZQ) per kg are effective against several intestinal cestodiases. The usually recommended single dose of PZQ in human taeniasis is 5 or 10 mg/kg. A study in T. saginata taeniasis showed a full efficacy at a dose of 2.5 mg/kg. A field study confirmed that a dose between 3.4 and 7.5 mg/kg was effective in expulsion T. solium tapeworms in man. A dose of 2.5 mg of PZQ per kg would be safer and more economical in population-oriented interventions aiming at control of T. solium taeniasis in man.
Topics: Animals; Humans; Praziquantel; Taeniasis
PubMed: 1980572
DOI: 10.1016/0001-706x(90)90046-3 -
Trends in Parasitology May 2022The anthelmintic praziquantel (PZQ) is an essential tool in controlling schistosomiasis, so reports of reduced PZQ efficacy are of great public health concern. Le Clec'h...
The anthelmintic praziquantel (PZQ) is an essential tool in controlling schistosomiasis, so reports of reduced PZQ efficacy are of great public health concern. Le Clec'h et al. recently identified a gene responsible for PZQ resistance in experimentally selected resistant Schistosoma mansoni. The importance of this locus in natural infections remains to be established.
Topics: Animals; Anthelmintics; Drug Resistance; Praziquantel; Schistosoma mansoni; Schistosomiasis mansoni
PubMed: 35246385
DOI: 10.1016/j.pt.2022.02.006