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Acta Tropica Jan 2018Soil-transmitted helminthiasis and schistosomiasis are major public health problems in Ethiopia. Mass deworming of at-risk population using a single dose administration...
Soil-transmitted helminthiasis and schistosomiasis are major public health problems in Ethiopia. Mass deworming of at-risk population using a single dose administration of 400mg albendazole (ABZ) or 500mg mebendazole (MBZ) for treatment of common intestinal worms and 40mg of praziquantel (PZQ) per kg body weight for treatment of schistosomiasis is one of the strategies recommended by World Health Organization (WHO) in order to control the morbidity of soil-transmitted helminthiasis and schistosomiasis. Since storage condition, climate, way of transportation and distribution route could all affect the quality of medicines, regular assessment by surveys is very critical to ensure the therapeutic outcome, to minimize risk of toxicity to the patient and resistance of parasites. Therefore, this study was conducted to assess the pharmaceutical quality of ABZ, MBZ and PZQ tablet brands commonly available in Jimma town (south west Ethiopia). Retail pharmacies (n=10) operating in Jimma town were selected using simple random sampling method. Samples of anthelminthic medicines available in the selected pharmacies were collected. Sample information was recorded and encompassed trade name, active ingredient name, manufacturer's name and full address, labeled medicine strength, dosage form, number of units per container, dosage statement, batch/lot number, manufacturing and expiry dates, storage information and presence of leaflets/package insert. Moreover, a first visual inspection was performed encompassing uniformity of color, uniformity of size, breaks, cracks, splits, embedded surface spots or visual contaminations. Finally, physico-chemical quality attributes investigated encompassed mass uniformity, quantity of active pharmaceutical ingredient (API), disintegration and dissolution, all following Pharmacopoeial test methods The physical characteristics of dosage form, packaging and labeling information of all samples complied with criteria given in the WHO checklists. The mass uniformity of tablets of each brand of ABZ, MBZ and PZQ complied with the pharmacopoeial specification limits, i.e no more than 2 individual masses >5% of average tablet weight, and none deviate by more than 10%. The quantity of APIs in all investigated tablet brands were within the 90-110% label claim (l.c.) limits, ranging between 95.05 and 110.09% l.c. Disintegration times were in line with the pharmacopoeial specification limit for immediate release (IR) tablets, ranging between 0.5 and 13min. However, the dissolution results (mean±SD, n=6) of one ABZ brand (i.e. Wormin, Q=59.21±0.99% at 30min) and two PZQ brands (i.e. Bermoxel, Q=63.43%±0.7 and Distocide, Q=62.43%±1.67, at 75min) showed poor dissolution, failing the United States Pharmacopoeia (USP) dissolution specification limit.
Topics: Albendazole; Anthelmintics; Ethiopia; Helminthiasis; Humans; Intestinal Diseases, Parasitic; Mebendazole; Praziquantel
PubMed: 29030043
DOI: 10.1016/j.actatropica.2017.10.006 -
European Journal of Pharmaceutics and... Sep 2019Schistosomiasis is a global disease of significant public health relevance. Only one racemic drug, praziquantel, characterized by low bioavailability, low water...
Schistosomiasis is a global disease of significant public health relevance. Only one racemic drug, praziquantel, characterized by low bioavailability, low water solubility and extensive first pass metabolism, is currently available. We studied a new praziquantel formulation (polymorph B), which is based on a racemic praziquantel crystalline polymorph (TELCEU01). Its in vitro activity was tested on newly transformed schistosomula (NTS) and adult Schistosoma mansoni. In vivo studies were conducted in mice harboring chronic S. mansoni infections. Pharmacokinetic (PK) profiles of R- and S-praziquantel and R- and S- polymorph B following oral administration with both formulations were generated by sampling mice at 30, 60, 240 min and 24 h post-treatment, followed by LC-MS/MS analysis. PK parameters were calculated using a non-compartmental analysis with a linear trapezoidal model. In vitro, commercial praziquantel and the polymorph B performed similarly on both NTS (IC = 2.58 and 2.40 µg/mL at 72 h) and adults (IC = 0.05 and 0.07 µg/mL at 72 h). Praziquantel showed higher in vivo efficacy with an ED of 58.75 mg/kg compared to an ED of 122.61 mg/kg for the polymorph B. The PK profiles of the two drugs exhibited differences: R-praziquantel showed an overall 40% higher area under the plasma drug concentration-time curve (AUC) (R-praziquantel = 3.42; R-polymorph B = 2.05 h*µg/mL) and an overall 30% lower apparent clearance (Cl/F) (R-praziquantel = 70.68 and R-polymorph B = 97.63 (mg)/(µg/mL)/h). Despite the lack of improved activity and PK properties of polymorph B against S. mansoni, here presented; research on pharmaceutical polymorphism remains a valid and cost-effective option for the development of new praziquantel formulations with enhanced properties such as increased solubility and/or dissolution.
Topics: Animals; Anthelmintics; Biological Availability; Crystallization; Disease Models, Animal; Female; Mice; Praziquantel; Schistosoma mansoni; Schistosomiasis mansoni; Solubility
PubMed: 31265895
DOI: 10.1016/j.ejpb.2019.06.029 -
Journal of Child Neurology Apr 2022To compare the efficacy of combined albendazole and praziquantel therapy vs albendazole monotherapy in a placebo-controlled, double-blinded, randomized trial in children... (Randomized Controlled Trial)
Randomized Controlled Trial
AIM
To compare the efficacy of combined albendazole and praziquantel therapy vs albendazole monotherapy in a placebo-controlled, double-blinded, randomized trial in children with persisting neurocysticercosis.
METHODS
Children with persistent neurocysticercosis were randomized into 3 groups-albendazole (n = 19), albendazole and praziquantel (n = 21), and placebo (n = 20)-for 30 days and followed up at 3 and 6 months for resolution and recurrence of seizures.
RESULTS
Mean age of children was 9.3 ± 2.9 years (range 3-14). At baseline, the majority of lesions were ring-enhancing (70%), colloidal (97%), with scolex (68%) and perilesional-edema (45%), and located in the parietal (58%) lobe. One case each in albendazole and placebo groups had a recurrence of seizure in the first month of treatment. The majority (62%) of children in the combination therapy group showed complete resolution of the persisting lesion at the end of 6 months compared to the albendazole alone group (26.3%, = .02). Percentage reduction in the lesion's mean area at 6 months was highest in the combination group compared with other groups ( = .006). Rate of calcification was identical in all 3 groups (10%). None of the patients required interruption of therapy.
CONCLUSION
Our study demonstrates the safety and efficacy of albendazole and praziquantel in combination for complete radiologic resolution in children with persistent neurocysticercosis when compared with albendazole monotherapy or placebo. The combination therapy did not result in increased seizure recurrence or adverse drug reaction compared with albendazole monotherapy.
Topics: Adolescent; Albendazole; Anthelmintics; Child; Child, Preschool; Drug Therapy, Combination; Humans; Neurocysticercosis; Praziquantel; Seizures
PubMed: 35213246
DOI: 10.1177/08830738221077762 -
Molecules (Basel, Switzerland) Mar 2022Solvent-assisted grinding (SAG) and solution slow evaporation (SSE) methods are generally used for the preparation of cocrystals. However, even by using the same...
Solvent-assisted grinding (SAG) and solution slow evaporation (SSE) methods are generally used for the preparation of cocrystals. However, even by using the same solvent, active pharmaceutical ingredient (API), and cocrystal coformer (CCF), the cocrystals prepared using the two methods above are sometimes inconsistent. In the present study, in the cocrystal synthesis of praziquantel (PRA) with polyhydroxy phenolic acid, including protocatechuic acid (PA), gallic acid (GA), and ferulic acid (FA), five different cocrystals were prepared using SAG and SSE. Three of the cocrystals prepared using the SAG method have the structural characteristics of carboxylic acid dimer, and two cocrystals prepared using the SSE method formed cocrystal solvates with the structural characteristics of carboxylic acid monomer. For phenolic acids containing only one phenolic hydroxyl group (ferulic acid), when preparing cocrystals with PRA by using SAG and SSE, the same product was obtained. In addition, the weak molecular interactions that were observed in the cocrystal are explained at the molecular level by using theoretical calculation methods. Finally, the in vitro solubility of cocrystals without crystal solvents and in vivo bioavailability of PRA-FA were evaluated to further understand the influence on the physicochemical properties of API for the introduction of CCF.
Topics: Biological Availability; Crystallization; Hydroxybenzoates; Praziquantel; Solubility
PubMed: 35335384
DOI: 10.3390/molecules27062022 -
International Journal For Parasitology Mar 2022Schistosomiasis, caused by schistosome parasites, is a neglected tropical disease affecting humans and animals. There is no vaccine available yet, and fear of upcoming...
Schistosomiasis, caused by schistosome parasites, is a neglected tropical disease affecting humans and animals. There is no vaccine available yet, and fear of upcoming resistance against the only widely used drug, praziquantel, is omnipresent. Previously, we showed that imatinib (Gleevec), an anticancer drug, affected schistosome physiology and caused the death of adult Schistosoma mansoni in vitro. Here, we present the first known evidence that one effect of imatinib is the induction of autophagy in S. mansoni. Furthermore, worms co-treated with imatinib and bafilomycin A1, a late-phase autophagy inhibitor, reversed imatinib-induced autophagy and its antischistosomal effects as revealed by phenotypic and molecular analyses.
Topics: Animals; Antineoplastic Agents; Autophagy; Imatinib Mesylate; Praziquantel; Schistosoma mansoni; Schistosomiasis mansoni
PubMed: 34838573
DOI: 10.1016/j.ijpara.2021.10.008 -
Parasites & Vectors Oct 2021Schistosomiasis is a debilitating and neglected tropical disease for which praziquantel (PZQ) remains the first-choice drug for treatment and control of the disease. In...
BACKGROUND
Schistosomiasis is a debilitating and neglected tropical disease for which praziquantel (PZQ) remains the first-choice drug for treatment and control of the disease. In our previous studies, we found that the patented compound DW-3-15 (patent no. ZL201110142538.2) displayed significant and stabilized antiparasitic activity through a mechanism that might be distinct from PZQ. Here, we investigated the antischistosomal efficacy of PZQ combined with DW-3-15 against schistosomula and adult worms of Schistosoma japonicum in vitro and in vivo, to verify whether there was a synergistic effect of the two compounds.
METHODS
The antischistosomal efficacy of PZQ combined with DW-3-15 in comparison with an untreated control and monotherapy group against schistosomula and adult worms was assessed both in vitro and in vivo. Parasitological studies, scanning electron microscopy, combination index, and histopathological analysis were used for the assessment.
RESULTS
The results showed significantly reduced viability of schistosomes, achieving 100% viability reduction for juveniles and males by combination chemotherapy using PZQ together with DW-3-15 in vitro. The combination index was 0.28, 0.27, and 0.53 at the higher concentration of PZQ combined with DW-3-15 against juveniles, males, and females, respectively, indicating that the two compounds display strong synergism. Scanning electron microscopy observations also demonstrated that the compound combination induced more severe and extensive alterations to the tegument and subtegument of S. japonicum than those with each compound alone. In vivo, compared with the single-compound-treated group, the group treated with the higher-dose combination demonstrated the best schistosomicidal efficacy, with significantly reduced worm burden, egg burden, and granuloma count and area, which was evident against schistosomula and adult worms.
CONCLUSIONS
Our study provides a potential novel chemotherapy for schistosomiasis caused by S. japonicum. It would improve the antischistosomal effect on schistosomula and adult worms of S. japonicum, and decrease individual dosages.
Topics: Animals; Drug Synergism; Drug Therapy, Combination; Female; Mice, Inbred ICR; Parasite Egg Count; Praziquantel; Schistosoma japonicum; Schistosomicides; Mice
PubMed: 34702326
DOI: 10.1186/s13071-021-05065-x -
Lancet (London, England) Jun 2024
Topics: Humans; Infant; Schistosomiasis; Anthelmintics; Praziquantel
PubMed: 38909612
DOI: 10.1016/S0140-6736(24)01302-3 -
Biomolecules Feb 2020Infections caused by and are classified as Group 1 biological carcinogen and it has been postulated that parasites produce oxysterol and estrogen-like metabolites that... (Review)
Review
Infections caused by and are classified as Group 1 biological carcinogen and it has been postulated that parasites produce oxysterol and estrogen-like metabolites that might be considered as initiators of infection-associated carcinogenesis. Chemotherapy for these helminthic infections relies on a single drug, praziquantel, (PZQ) that mainly targets the parasite. Additionally, PZQ has some major drawbacks as inefficacy against juvenile form and alone it is not capable to counteract pathologies associated to infections or prevent carcinogenesis. There is an urgent need to develop novel therapeutic approaches that not only target the parasite but also improve the pathologies associated to infection, and ultimately, counteract or/and prevent the carcinogenesis processes. Repurposing the drug in combination of compounds with different modes of action is a promising strategy to find novel therapeutics approaches against these helminthic infections and its pathologies. Here, we emphasized that using antioxidants either alone or combined with anthelmintic drugs could ameliorate tissue damage, infection-associated complications, moreover, could prevent the development of cancer associated to infections. Hence, antioxidants represent a potential adjuvant approach during treatment to reduce morbidity and mortality. Despite the success of some strategies, there is a long way to go to implement novel therapies for schistosomiasis.
Topics: Animals; Anthelmintics; Antioxidants; Drug Discovery; Drug Repositioning; Drug Therapy, Combination; Humans; Neoplasms; Opisthorchiasis; Opisthorchis; Praziquantel; Schistosoma; Schistosomiasis
PubMed: 32106428
DOI: 10.3390/biom10030350 -
Biochemical Pharmacology Jul 2014Praziquantel (PZQ), prescribed as a racemic mixture, is the most readily available drug to treat schistosomiasis. In the present study, ultra-performance liquid...
Praziquantel (PZQ), prescribed as a racemic mixture, is the most readily available drug to treat schistosomiasis. In the present study, ultra-performance liquid chromatography coupled with electrospray ionization quadrupole time-of-flight mass spectrometry (UPLC-ESI-QTOFMS) based metabolomics was employed to decipher the metabolic pathways and enantioselective metabolic differences of PZQ. Many phase I and four new phase II metabolites were found in urine and feces samples of mice 24h after dosing, indicating that the major metabolic reactions encompassed oxidation, dehydrogenation, and glucuronidation. Differences in the formation of all these metabolites were observed between (R)-PZQ and (S)-PZQ. In an in vitro phase I incubation system, the major involvement of CYP3A, CYP2C9, and CYP2C19 in the metabolism of PZQ, and CYP3A, CYP2C9, and CYP2C19 exhibited different catalytic activity toward the PZQ enantiomers. Apparent Km and Vmax differences were observed in the catalytic formation of three mono-oxidized metabolites by CYP2C9 and CYP3A4 further supporting the metabolic differences for PZQ enantiomers. Molecular docking showed that chirality resulted in differences in substrate location and conformation, which likely accounts for the metabolic differences. In conclusion, in silico, in vitro, and in vivo methods revealed the enantioselective metabolic profile of praziquantel.
Topics: Administration, Oral; Animals; Aryl Hydrocarbon Hydroxylases; Chromatography, High Pressure Liquid; Cytochrome P-450 CYP3A; Cytochrome P-450 Enzyme System; Feces; Isoenzymes; Kinetics; Male; Metabolic Detoxication, Phase I; Metabolic Detoxication, Phase II; Metabolome; Mice; Molecular Docking Simulation; Praziquantel; Protein Conformation; Schistosomicides; Spectrometry, Mass, Electrospray Ionization; Stereoisomerism; Substrate Specificity
PubMed: 24821110
DOI: 10.1016/j.bcp.2014.05.001 -
Frontiers in Immunology 2022The new WHO Roadmap for Neglected Tropical Diseases targets the global elimination of schistosomiasis as a public health problem. To date, control strategies have... (Review)
Review
The new WHO Roadmap for Neglected Tropical Diseases targets the global elimination of schistosomiasis as a public health problem. To date, control strategies have focused on effective diagnostics, mass drug administration, complementary and integrative public health interventions. Non-mammalian intermediate hosts and other vertebrates promote transmission of schistosomiasis and have been utilized as experimental model systems. Experimental animal models that recapitulate schistosomiasis immunology, disease progression, and pathology observed in humans are important in testing and validation of control interventions. We discuss the pivotal value of these models in contributing to elimination of schistosomiasis. Treatment of schistosomiasis relies heavily on mass drug administration of praziquantel whose efficacy is comprised due to re-infections and experimental systems have revealed the inability to kill juvenile schistosomes. In terms of diagnosis, nonhuman primate models have demonstrated the low sensitivity of the gold standard Kato Katz smear technique. Antibody assays are valuable tools for evaluating efficacy of candidate vaccines, and sera from graded infection experiments are useful for evaluating diagnostic sensitivity of different targets. Lastly, the presence of Schistosomes can compromise the efficacy of vaccines to other infectious diseases and its elimination will benefit control programs of the other diseases. As the focus moves towards schistosomiasis elimination, it will be critical to integrate treatment, diagnostics, novel research tools such as sequencing, improved understanding of disease pathogenesis and utilization of experimental models to assist with evaluating performance of new approaches.
Topics: Animals; Neglected Diseases; Praziquantel; Schistosoma; Schistosomiasis; Vaccines
PubMed: 35592327
DOI: 10.3389/fimmu.2022.846108