Slow-release praziquantel for dogs: presentation of a new formulation for echinococcosis control

Abstract

BackgroundEchinococcosis is a serious, zoonotic, parasitic disease with worldwide distribution. According to a epidemiological survey in 2012 in China, there are 20,000 infected patients and more than 50 million people at the risk. As the dog is the main, definitive host, the Government of China encourages monthly praziquantel treatment of every dog. However, this is difficult to achieve in geographically challenging areas, such as the Tibetan plateau, where there are also many dogs without owners. To overcome these problems, we investigated the transmission blocking capacity of a slow-release formulation of praziquantel administered by subcutaneous injection.MethodsThe impact of a slow-release preparation of two pharmacokinetically stereoselective praziquantel enantiomers, i.e., R-(−)-praziquantel (R-PZQ) and S-(+)-praziquantel (S-PZQ) absorbed into a biodegradable polymer was studied in beagle dogs (N = 6). The preparation was given by subcutaneous injection using a single dose of 100 mg/kg. Chiral-selective, high-performance liquid chromatography (HPLC) and high-resolution mass spectrometry (HRMS) were applied to measure the praziquantel enantiomers in the plasma of the dogs. The lower limit for estimating plasma concentrations accurately for R-PZQ was 4 ng/ml and for S-PZQ 20 ng/ml. The pharmacokinetic parameters were calculated by a noncompartmental analysis model using Drug Analyze System (DAS) software 2.0. The SPSS 19.0 software was used for statistical analysis, and the statistical comparison between enantiomers was assessed using the two-tailed t-test.ResultsTwo hours after administration, peak concentrations of R-PZQ and S-PZQ: 321 ± 26 and 719 ± 263 ng/ml, respectively, were achieved. After 180 days, the average plasma concentration of R-PZQ in the six dogs had decreased to 13 ng/ml. The average concentration value of S-PZQ was higher than that of R-PZQ in the first 90-day period but fell afterwards and could not be accurately estimated when dropping below 20 ng/ml (the lower methodological limit for this enantiomer). Taking all the dogs into account, the average maximum concentration (Cmax) of S-PZQ in plasma over the first 3 months was higher than that of R-PZQ by 114.0% (P < 0.05), while the average mean retention time (MRT) of R-PZQ in plasma was higher than that of S-PZQ by 96.3% (P < 0.05).ConclusionsPraziquantel given as an in situ slow-release formulation by subcutaneous injection resulted in concentrations of the active principle in beagle dogs, which should be capable of resisting new Echinococcus infections for at least 6 months. The new formulation of praziquantel represents a potential, alternative way of presenting medication against tapeworm infections in dogs.Electronic supplementary materialThe online version of this article (10.1186/s40249-017-0357-4) contains supplementary material, which is available to authorized users.

The effects of dog management on Echinococcus spp. prevalence in villages on the eastern Tibetan Plateau, China

“…Tibetans frequently expressed their concerns about the potential negative side effects of the drug during surveys in villages. The possible use of slow release praziquantel [39] may be a better choice for future large-scale implementation though such formulations require further assessment.…”

Chromatographic Quantification of Ivermectin and Pranziquantel in the Tablets Using Stability Indicating RP-HPLC Method

“…In dogs, horses and cats, praziquantel is prescribed to treat tapeworm infections, pancreas fluke and blood flukes. [9][10][11] Praziquantel is chemically known as (RS)-2-(Cyclohexylcarbonyl)-1,2,3,6,7,11b-hexahydro-4H-pyrazino[2,1-a]isoquinolin-4-one ( Figure 2). Ivermectin and praziquantel combination is available in paste form (Equimax paste with strength 14.03% praziquantel and 1.87% ivermectin) and tablet dosage form (Ipraz tablet with strength 2 mg ivermectin and 50 mg praziquantel).…”

Hydatid Cyst With Focus on Manifestations, Diagnosis, and Management: Review

“…• Prevent dogs from feeding on infected sheep [19,33] • The limiting of home cattle butchers [34] • Avoidance of any food or water that may be contaminated by dog's feces [25,35] • Handwashing with soap and water after handling dogs [25] • Vaccination of cattle with EG95 vaccine to interrupt the life cycle of E. granulosus [36][37][38] • Dogs can be terminated using praziquantel every 6 weeks [37,39] • Not to contact with wild animals such as foxes and stray dogs [25].…”