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.