Stereoselective Pharmacokinetics and Residue Depletion of Praziquantel and Its Metabolites, 4-Hydroxypraziquantel Enantiomers, in Swine.

Praziquantel (PZQ) is administered as a racemic mixture during swine production to treat parasitic diseases. Despite its widespread application, the pharmacokinetics, residue depletion, bioactivity, and toxicity of PZQ enantiomers in swine remain largely unknown. In this study, a systematic investigation of the pharmacokinetics, tissue distribution, and residue depletion of PZQ, its major metabolites (trans- and cis-4-OH-PZQ), and their enantiomers was conducted in swine. The findings indicated that PZQ was absorbed and metabolized rapidly. In swine plasma, the concentrations of S-PZQ, S-trans-4-OH-PZQ, and R-cis-4-OH-PZQ were higher than those of their respective enantiomers. The three analytes exhibited significant tissue distribution and stereoselectivity in 10 swine tissues. Notably, the two enantiomers of PZQ demonstrated comparable tissue concentrations except in the liver and lung. Moreover, the concentrations of S-trans-4-OH-PZQ and R-cis-4-OH-PZQ were higher than those of their respective enantiomers in the 10 tissues. This study has significant implications for the development of rational dosing strategies, reducing drug usage, and minimizing side effects, as well as accurately assessing the risks associated with PZQ administration and, by extension, other chiral drugs. Furthermore, it lays a theoretical foundation for the future use of the active enantiomer, R-PZQ.

Simultaneous determination of praziquantel and its main metabolites in the tissues of black goats and their residue depletion.

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 trans- and cis-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.

Pharmacokinetics, Activity, and Residue Elimination of R- and S-Diclazuril in Broiler Chickens.

Diclazuril (DIC) is widely used as a racemic mixture to prevent and treat coccidiosis in farm animals, while the pharmacokinetics, bioactivity, and toxicity of DIC enantiomers are not known at all. This study first established a simple, sensitive, and reliable liquid chromatography tandem mass spectrometry method for separation of R-DIC and S-DIC and their analyses. Then, it was applied to investigate the stereoselective pharmacokinetics and residual elimination of individual enantiomers, and their anticoccidial activity was also evaluated in broiler chickens. The results indicated that the area under the concentration-time curve (AUC) and elimination half-life (t1/2ß) were significantly different (p < 0.05) for two enantiomers in chicken plasma. The AUC and t1/2ß of S-DIC were approximately 2 and 1.4 times those of R-DIC, respectively. The residual elimination of DIC enantiomers in chicken tissues was also stereoselective. The concentrations of S-DIC in chicken muscle and liver were greater than those of R-DIC, and it is the opposite in the kidney. There was no significant difference (p > 0.05) in the anticoccidial activity of racemate and enantiomers when a single enantiomer in feed was added above 0.5 mg kg-1. However, the anticoccidial activity of R-DIC (0.25 mg kg-1) was significantly higher (p < 0.05) than that of S-DIC (0.25 mg kg-1) in the diet. It should be mentioned that in chicken small intestine and cecum, the enantiomerization rate of each enantiomer in the infection group was faster than that in the uninfected group.