Praziquantel (DB01058): A Comprehensive Pharmacological and Clinical Monograph

Executive Summary

Praziquantel is a pyrazino-isoquinoline derivative that stands as a cornerstone of global public health, recognized on the World Health Organization's List of Essential Medicines for its role as a broad-spectrum anthelmintic agent. It is the drug of choice for the treatment of schistosomiasis and a first-line therapy for a wide array of other trematode (fluke) and cestode (tapeworm) infections. Despite over four decades of widespread clinical use, its precise molecular mechanism of action remains to be fully elucidated, though the current consensus centers on its ability to rapidly and catastrophically disrupt calcium homeostasis within the parasite. This leads to spastic paralysis and severe damage to the parasite's outer surface, the tegument, which facilitates clearance by the host's immune system. The commercially available formulation is a racemic mixture, with the anthelmintic activity residing exclusively in the (R)-enantiomer, a fact that has significant implications for drug formulation, patient tolerability, and future development. Praziquantel exhibits a complex pharmacokinetic profile characterized by rapid absorption, extensive first-pass metabolism mediated by the polymorphic cytochrome P450 system, and a profound food effect that can increase bioavailability up to four-fold. This inherent variability, combined with a significant potential for drug-drug interactions, necessitates careful clinical management. The safety profile of praziquantel is largely favorable for most indications, but adverse effects are directly correlated with parasite burden, and treatment of neurocysticercosis presents unique and severe risks related to the host's inflammatory response to dying intracerebral parasites. This monograph provides an exhaustive analysis of praziquantel's chemical properties, pharmacology, pharmacokinetics, clinical applications, and safet