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Biomedica : Revista Del Instituto... Mar 2022Praziquantel (PZQ) is the only commercially available drug for schistosomiasis. The current shortage of alternative effective drugs and the lack of successful preventive...
INTRODUCTION
Praziquantel (PZQ) is the only commercially available drug for schistosomiasis. The current shortage of alternative effective drugs and the lack of successful preventive measures enhance its value. The increase in the prevalence of PZQ resistance under sustained drug pressure is, therefore, an upcoming issue.
OBJECTIVE
To overcome the tolerance to PZQ using nanotechnology after laboratory induction of a Schistosoma mansoni isolate with reduced sensitivity to the drug during the intramolluscan phase.
MATERIALS AND METHODS
Shedding snails were treated with PZQ doses of 200 mg/kg twice/ week followed by an interval of one week and then repeated twice in the same manner. The success of inducing reduced sensitivity was confirmed in vitro via the reduction of cercarial response to PZQ regarding their swimming activity and death percentage at different examination times.
RESULTS
Oral treatment with a single PZQ dose of 500 mg/kg in mice infected with cercariae with reduced sensitivity to PZQ revealed a non-significant reduction (35.1%) of total worm burden compared to non-treated control mice. Orally inoculated PZQ-encapsulated niosomes against S. mansoni with reduced sensitivity to PZQ successfully regained the pathogen's sensitivity to PZQ as evidenced by measuring different parameters in comparison to the non-treated infected animals with parasites with reduced sensitivity to PZQ. The mean total worm load was 1.33 ± 0.52 with a statistically significant reduction of 94.09% and complete eradication of male worms. We obtained a remarkable increase in the percentage reduction of tissue egg counts in the liver and intestine (97.68% and 98.56%, respectively) associated with a massive increase in dead eggs and the complete absence of immature stages.
CONCLUSION
PZQ-encapsulated niosomes restored the drug sensitivity against laboratory-induced S. mansoni adult worms with reduced sensitivity to PZQ.
Topics: Animals; Drug Resistance; Liposomes; Male; Mice; Praziquantel; Schistosoma mansoni; Snails
PubMed: 35471171
DOI: 10.7705/biomedica.5913 -
Parasitology Research Dec 2011Praziquantel, due to high efficacy, excellent tolerability, few and transient side effects, simple administration, and competitive cost, is virtually the only drug of... (Review)
Review
Praziquantel, due to high efficacy, excellent tolerability, few and transient side effects, simple administration, and competitive cost, is virtually the only drug of choice for treatment of human schistosomiasis. Treatment of schistosomiasis has shown great advances with the introduction of the drug into the therapeutic arsenal in areas that are endemic for the parasite. However, the drug presents various efficacies against different developmental stages of schistosomes, appearing an oddity intermitted mode. The present review article reviews the effects and mechanism of action of praziquantel against schistosomes briefly and suggests the research on this oddity phenomenon.
Topics: Animals; Humans; Praziquantel; Schistosoma; Schistosomiasis; Schistosomicides
PubMed: 21984370
DOI: 10.1007/s00436-011-2670-3 -
Experimental Parasitology Aug 2023
Topics: Animals; Praziquantel; Schistosomicides; Liposomes; Nanoparticles; Schistosoma mansoni
PubMed: 37285898
DOI: 10.1016/j.exppara.2023.108552 -
Lancet (London, England) Mar 1980
Comparative Study
Topics: Dose-Response Relationship, Drug; Humans; Isoquinolines; Praziquantel; Schistosoma haematobium; Schistosoma japonicum; Schistosoma mansoni; Schistosomiasis
PubMed: 6102634
DOI: No ID Found -
Expert Review of Clinical Pharmacology Apr 2020Effective medicines exist to address global health challenges including Neglected Tropical Diseases (NTD) and Noncommunicable Diseases (NCD) however these are often... (Review)
Review
INTRODUCTION
Effective medicines exist to address global health challenges including Neglected Tropical Diseases (NTD) and Noncommunicable Diseases (NCD) however these are often unavailable and unaffordable. To date, little literature exists comparing medicine unavailability across broad disease areas.
AREAS COVERED
Using insulin and praziquantel as tracer medicines this review aims to demonstrate that separating global health governance agendas for NCDs and NTDs ultimately impacts the effectiveness of coalitions for access for the poorest populations. Electronic literature searches were performed through Science Direct, PubMed, and Google Scholar (March-May2017 and updated in September-December2019) using keywords from Shiffman's framework; NCDs; NTDs; and for each medicine. Best practice from each area was analyzed.
EXPERT OPINION
Many actors responded to the London Declaration which reinforced praziquantel's central role in control and elimination of schistosomiasis whereas access to affordable insulin emerged secondary to framing around prevention and management of diabetes. For insulin key stakeholders are not aligned around access. The position taken by pharmaceutical companies as donors versus commercial actors was critical to sustainable affordable access to these medicines. Integrated access models for low resource populations need shared pathways given the increasing need for essential medicines in the context of Universal Health Coverage.
Topics: Anthelmintics; Diabetes Mellitus; Global Health; Health Services Accessibility; Humans; Hypoglycemic Agents; Insulin; Neglected Diseases; Noncommunicable Diseases; Praziquantel; Schistosomiasis; Tropical Medicine
PubMed: 32155094
DOI: 10.1080/17512433.2020.1740589 -
Food Additives & Contaminants. Part A,... Apr 2022Praziquantel (PZQ) is a pyrazino-isoquinoline compound with broad spectrum of activity against parasitic trematodes and cestodes, and a key veterinary drug in the...
Praziquantel (PZQ) is a pyrazino-isoquinoline compound with broad spectrum of activity against parasitic trematodes and cestodes, and a key veterinary drug in the parasitic disease control field. However, PZQ residues caused by non-conforming or excessive use in food-producing animals may pose a serious threat to human health. Herein, a simple, sensitive and reproducible LC-MS/MS method was developed for the simultaneous determination of praziquantel and - and -4-hydroxypraziquantel in black goat tissues to guide the reasonable use of PZQ. The mean recoveries for three target analytes were 71.2 ∼ 117.6%, and the limits of quantification were 1.0 μg/kg. Twenty-five healthy black goats were administered a single dose of praziquantel tablets at a dose of 35 mg/kg of body weight for residue elimination study, The results revealed that praziquantel and 4-hydroxypraziquantel were rapidly depleted in goat tissues and the elimination half-lives did not exceed 1 day in all tissues except for muscle and lung. It provides guidance for the establishment of maximum residue limit of praziquantel in goat.
Topics: Animals; Anthelmintics; Chromatography, Liquid; Goats; Muscles; Praziquantel; Tandem Mass Spectrometry
PubMed: 35394409
DOI: 10.1080/19440049.2022.2032380 -
Acta Tropica May 2003Praziquantel (PZQ) is the safest of all anti-helminthics and now forms the backbone for all national control programs against schistosomiasis (Med. Res. Rev. 3 (1983)... (Review)
Review
Praziquantel (PZQ) is the safest of all anti-helminthics and now forms the backbone for all national control programs against schistosomiasis (Med. Res. Rev. 3 (1983) 147-200; Bull. WHO 57 (1979) 767-771; Wegner, D.H.G, Therapeutic Drugs (1991), Churchill Livingstone; Adv. Intern. Med. 32 (1987) 193-206; Drugs 42 (1991) 379-405; Pharmac. Ther. 68 (1995) 35-85; Ann. Intern. Med. 110 (1989) 290-296). Despite its lack of known toxicity, the drug was not tested on pregnant or lactating women prior to release. It is currently listed as Pregnancy Category B by the US FDA, which is a drug presumed safe based in animal studies. Unfortunately, this has been interpreted by most national control programs and WHO (1998) to exclude lactating and pregnant women from treatment. In fact, some experts advocate excluding adolescent girls from mass treatment campaigns over this issue. As a result, a large number of women living in endemic countries are currently left untreated or have treatment significantly delayed. A review of the current known toxicology of PZQ, combined with over two decades of clinical experience with this drug, suggest very low potential for adverse effects on either the mother or her unborn child. In contrast, significant animal and human data are presented in this review that suggest both the pregnant woman and her unborn fetus suffer morbid sequella from schistosomiasis. A double-blind placebo-controlled trial that could resolve this issue would require a very large and expensive study and in light of the above facts might not now be ethically appropriate. The author concludes that pregnant women should be treated with PZQ, that women of childbearing age should be included in all mass treatment programs and that lactating women are not systematically excluded from treatment.
Topics: Anthelmintics; Female; Humans; Lactation; Praziquantel; Pregnancy; Schistosomiasis
PubMed: 12745136
DOI: 10.1016/s0001-706x(03)00033-0 -
Zhongguo Xue Xi Chong Bing Fang Zhi Za... Jul 2017To investigate the pharmacokinetics and relative bioavailability of praziquantel injection in buffaloes in contrast to praziquantel tablet. A single oral... (Comparative Study)
Comparative Study
To investigate the pharmacokinetics and relative bioavailability of praziquantel injection in buffaloes in contrast to praziquantel tablet. A single oral administration of praziquantel tablet at a dose of 20 mg/kg or intramuscular administration of praziquantel injection at a dose of 10 mg/kg was performed in six healthy adult buffalos according to a twoperiod crossover design. The praziquantel concentration in plasma was determined by a high performance liquid chromatography (HPLC) method. The pharmacokinetic parameters were calculated by non-compartmental analysis. The main pharmacokinetic parameters of praziquantel tablet were as follows: = (0.60±0.29)h, = (0.57±0.37)μg/ml, = (0.70±0.42)h, = (0.80±0.70) (μg/ml)·h. The main pharmacokinetic parameters of praziquantel injection were as follows: = (0.65± 0.49)h, = (3.82±1.17)μg/ml, = (1.00±0.73)h, = (1.61±0.89) (μg/ml)·h. The relative bioavailability of praziquantel injection was 402.5% in contrast to praziquantel tablet. The praziquantel injection has pharmacokinetic characteristics of rapid absorption, high bioavailability and extensive distribution, and the clinical recommended dosage of praziquantel injection is 10 mg/kg.
Topics: Administration, Oral; Animals; Biological Availability; Buffaloes; Cross-Over Studies; Injections, Intramuscular; Praziquantel; Tablets
PubMed: 29508574
DOI: 10.16250/j.32.1374.2017032 -
Medecine Tropicale : Revue Du Corps de... 1997
Topics: Antiplatyhelmintic Agents; Humans; Patient Selection; Praziquantel; Trematode Infections
PubMed: 9513143
DOI: No ID Found -
ChemMedChem Sep 2023Praziquantel (PZQ) is an essential anthelmintic drug recently established to be an activator of a Transient Receptor Potential Melastatin (TRPM ) ion channel in...
Praziquantel (PZQ) is an essential anthelmintic drug recently established to be an activator of a Transient Receptor Potential Melastatin (TRPM ) ion channel in trematode worms. Bioinformatic, mutagenesis and drug metabolism work indicate that the cyclohexyl ring of PZQ is a key pharmacophore for activation of trematode TRPM , as well as serving as the primary site of oxidative metabolism which results in PZQ being a short-lived drug. Based on our recent findings, the hydrophobic cleft in schistosome TRPM defined by three hydrophobic residues surrounding the cyclohexyl ring has little tolerance for polarity. Here we evaluate the in vitro and in vivo activities of PZQ analogues with improved metabolic stability relative to the challenge of maintaining activity on the channel. Finally, an estimation of the respective contribution to the overall activity of both the parent and the main metabolite of PZQ in humans is reported.
Topics: Humans; Animals; Praziquantel; Parasites; Transient Receptor Potential Channels; TRPM Cation Channels; Anthelmintics; Schistosoma mansoni
PubMed: 37272317
DOI: 10.1002/cmdc.202300140