Validated capillary electrophoretic method for the enantiomeric quality control of R-praziquantel.

The enantiomers of praziquantel, the drug of choice in schistosomiasis, were separated by electrokinetic chromatography with cyclodextrins. Nine anionic cyclodextrins were screened for their ability to discriminate between the uncharged enantiomers. Seven investigated selectors presented chiral interactions with the enantiomers, these cases being interpreted in terms of stability constants and complex mobilities. The best results were delivered by sulfated-ß-cyclodextrin, where quasi-equal stability constants were accompanied by extreme selectivity values and was explained on the basis of highly different mobilities of the transient diastereomeric complexes. Since the enantiomer migration order was unfavorable, a simple polarity switch was employed (detection end at anode), which apart from migration order reversal, also resulted in extreme resolution values (Rs > 35) and increased migration times. After optimization (50 mM phosphate buffer pH 2.0, supplied with 15 mM sulfated-ß-cyclodextrin, 15 kV, capillary temperature 25°C, short-end injection with 50 mbar × 2 s), analysis time under 10 min were obtained, while still maintaining high resolution (Rs > 10). The method was validated according to the ICH guidelines and application of the method was tested on in-house synthetized R-praziquantel batches and on commercial, combination tablets containing racemic mixture of the drug.

Efficacy of moxidectin against cyathostomins after long-term use in a large herd of draught horses with a high stocking density.

This study was undertaken to determine whether resistance to moxidectin had developed in a large herd of draught horses, maintained on a small acreage, which had been routinely treated with moxidectin for five years. Faeces were collected for egg counts immediately before moxidectin gel was administered orally, and seven, 30, 60 and 90 days later. The faecal egg counts were significantly reduced at seven and 30 days after treatment, but were not significantly different from pretreatment counts at 60 and 90 days after treatment. There was no evidence of resistance having developed.

Efficacy of China-made praziquantel for treatment of Schistosomiasis haematobium in Africa: A randomized controlled trial.

BACKGROUND: In the roadmap on the neglected tropical diseases (NTD) the World Health Organization (WHO) aims at attaining at least 75% coverage of preventive chemotherapy in pre-school and school-age children by 2020. A randomized controlled trial was used to compare the effectiveness of praziquantel in treating Schistosoma haematobium in Africa using two different sources for the drug, Merck Limited Partnership (KgaA), Germany and Nanjing Pharmaceutical Factory (NPF), China. METHODS: More than 6,000 participants testing positive for S. haematobium infection were enrolled from three villages (shehias) situated in the northern, middle and southern part of Pemba Island, Zanzibar. Applying criteria of inclusion and exclusion, resulted in a study population of 152 people (84 males, 68 females). A randomized controlled trial was conducted assigning participants to either praziquantel from NPF or Merck KGaA. After one month, the cure rate of S. haematobium and adverse events were compared to evaluate effectiveness. The ratio of male to female, the ratio of light/high infection intensity, and the average value of age were calculated between the two drug manufacturers. Chi-squared test and T-test were used for consistency analysis. RESULTS: Out of the total of 73 cases receiving praziquantel from NPF, the cure rate achieved was 97.3% (73/75), while the 74 cases receiving the drug from Merck KgaA reached a similar cure rate (96.1% or 74/77). There was no significant difference between the two outcomes (χ2 = 0.003, P = 0.956). Among the 75 patients treat, only one (a 16-years old female student), who had received the drug made in China had slight adverse reactions manifested as dizziness, headache and abdominal pain. CONCLUSION: The efficacy of China-made praziquantel does not differ significantly from praziquantel made by Merck KGaA in Germany. TRIAL REGISTRATION: ClinicalTrials.gov, NCT03133832.

Accuracy of the WHO praziquantel dose pole for large-scale community treatment of urogenital schistosomiasis in northern Mozambique: Is it time for an update?

BACKGROUND: A pioneering strategy developed by the World Health Organization (WHO) for the control of schistosomiasis was the concept of a height-based dose pole to determine praziquantel (PZQ) dosing in large-scale treatment campaigns. However, some recent studies have shown variable accuracy for the dose pole in terms of predicting correct mg/Kg dosing, particularly for treatment of adults. According to the WHO, 91 million adults in 52 countries are targeted to be treated by 2020. METHODS/PRINCIPAL FINDINGS: The present study aimed to test the accuracy of the dose pole in determining PZQ dosage by comparing the number of tablets determined by the dose pole with the number of tablets determined according to total body weight. The analysis included height-for-weight data from 9,827 school-aged children (SAC) and adults from 42 villages in the province of Cabo Delgado in Mozambique. The results revealed that of the 7,596 SAC, 91.8% has received an appropriate dose (30-60mg/Kg), 6% received an insufficient dose (<30mg/Kg) and 2% an excessive dose (> 60mg/Kg). On the other hand, 13.7% out of 2,231 adults were treated inaccurately with 13.5% receiving an insufficient dose and 0.2% an excessive dose. When the percentage of insufficient dosing was disaggregated by gender, the frequency of adult females who were underdosed reached 18.3% versus 10.8% of adult males. Of note, Adult females aged 21-55 years were found to have an underdose frequency of 21.3%, compared to 11.8% of adult males in the same age range. The performance of a proposed modified dose pole was compared using the same dataset of adult Mozambicans. The results showed that the modified dose pole reduced the underdose frequency among adults from 13.5% to 10.4%, and subsequently increased the percentage of optimal dosing from 33.7% to 45.3%. CONCLUSIONS: Our findings highlight the need to update the WHO-dose pole to avoid administration of insufficient PZQ doses to adults and therefore minimize the potential emergence of PZQ-resistant strains. TRIAL REGISTRATION: International Standard Randomized Controlled Trial registry under ISRTC number 14117624.

Quality of anthelminthic medicines available in Jimma Ethiopia.

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.

Praziquantel--quality, dosages and markers of resistance.

The fourth and last meeting of Concerted Action on Praziquantel (PZQ), sponsored by the European Commission, was held in Rome, Italy from 31 March to 1 April, 2001. Highlights of the meeting were new findings on the quality of generic drugs, an initiative to promote the Africa-wide distribution of PZQ and new results in the search for markers of PZQ-resistant schistosomes.

Efficacy of praziquantel in the treatment of green sea turtles with spontaneous infection of cardiovascular flukes.

OBJECTIVE: To assess the efficacy of praziquantel as a treatment for cardiovascular flukes in turtles. PROCEDURE: Six green sea turtles (Chelonia mydas) spontaneously infected with cardiovascular flukes (Digenea: Spirorchiidae) were treated orally with praziquantel, and necropsied 3 or 7 days later to look for flukes in the heart and major blood vessels. Six similar animals were maintained as untreated controls. RESULTS: Absence of flukes in treated, but not control turtles, indicated that a one day course of treatment at a dose rate of 3 x 50 mg/kg body weight is effective. CONCLUSION: This result should be of value for preventing disease in wild caught green turtles introduced into farms or aquaria.