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

Praziquantel (PZQ) is administered as a racemic mixtureduringswine production to treat parasitic diseases. Despite its widespreadapplication, the pharmacokinetics, residue depletion, bioactivity,and toxicity of PZQ enantiomers in swine remain largely unknown. Inthis study, a systematic investigation of the pharmacokinetics, tissuedistribution, and residue depletion of PZQ, its major metabolites(trans- and cis-4-OH-PZQ), and theirenantiomers was conducted in swine. The findings indicated that PZQwas absorbed and metabolized rapidly. In swine plasma, the concentrationsof S-PZQ, S-trans-4-OH-PZQ, and R-cis-4-OH-PZQ werehigher than those of their respective enantiomers. The three analytesexhibited significant tissue distribution and stereoselectivity in10 swine tissues. Notably, the two enantiomers of PZQ demonstratedcomparable tissue concentrations except in the liver and lung. Moreover,the concentrations of S-trans-4-OH-PZQand R-cis-4-OH-PZQ were higher thanthose of their respective enantiomers in the 10 tissues. This studyhas significant implications for the development of rational dosingstrategies, reducing drug usage, and minimizing side effects, as wellas accurately assessing the risks associated with PZQ administrationand, by extension, other chiral drugs. Furthermore, it lays a theoreticalfoundation for the future use of the active enantiomer, R-PZQ.

Automated summary

This study systematically investigated the pharmacokinetics, tissue distribution, and residue depletion of praziquantel in swine. The findings have important implications for rational dosing strategies, reducing drug usage and side effects, accurately assessing the risks associated with praziquantel administration, and future use of the active enantiomer R-PZQ.