Praziquantel: a pyrazino-isoquinolein derivative

Introduction

Praziquantel is a pyrazino-isoquinolein derivative from the thioxantonic group used as a broad anthelmintic spectrum. Specifically, it is known as a treatment of trematodes and cestodes infections such as schistosomiasis, taeniasis, and cysticercosis. The efficacy of Praziquantel in treating parasitic flatworm infection at a low cost (~US$0.20 drug cost to treat a child) makes it integral to WHO's plan to eliminate schistosomiasis by 2030. Despite being approved since 1980, the exact mechanism of action is yet to be elucidated.

Chemical property

Praziquantel is a white powder with a bitter taste that is stable under normal storage conditions. It is practically insoluble in water but in ethanol and other organic solvents[1]. Currently, Praziquantel is on the market as a pill, in dosages of 150, 500 and 600 mg, and the posology is made according to the patient body weight. PZQ is classified as a Group II BCS member (Biopharmaceutics Classification System), a drug with low solubility and high permeability in the gastrointestinal tract (GIT), so the dissolution rate is the limiting factor of its absorption and one of the main reasons for the high doses. The optimization of the dissolution rate of this class of drugs is, therefore, an essential and challenging aspect in the development of new formulations.

Indications

Praziquantel, a pyrazinoisoquinoline derivative developed in the early 1970s, has broad activity against trematodes and cestodes but not nematodes. All Schistosoma spp. that infect humans are susceptible. The drug also has activity against the trematodes C. sinensis, Dicrocoelium dendriticum, Echinostoma spp., F. buski, H. heterophyes, Metagonimus yokogawai, Metorchis conjunctus, Nanophyetus salmincola, Opisthorchis viverrini and Paragonimus westermani and other Paragonimus spp. Fasciola hepatica does not appear adequately treated with Praziquantel; bithionol is used instead. Praziquantel is effective in treating adult cestodes, including D. latum and other Diphyllobothrium spp., D. caninum, H. nana, Hymenolepis diminuta, T. saginata and T. solium. It has been used successfully to treat neurocysticercosis (larval T. solium) but is not helpful in echinococcosis. The drug has several actions, including promoting calcium influx and parasite muscle contraction, causing vacuolization and bleb formation in the helminth tegument, and activating host defences [2].

Side effects

Praziquantel is available as 600 mg tablets that are nearly insoluble in water. There is good oral absorption, 80% protein binding and rapid first-pass metabolism. The half-life is 1.5 hours. About 80% of the drug is excreted in the urine. Side effects are common but transient, including headache, dizziness, nausea, vomiting, and abdominal pain. Fever and rashes are occasionally seen.

References

[1] Vinícius Barros Ribeiro da Silva . “Medicinal chemistry of antischistosomal drugs: Praziquantel and oxamniquine.” Bioorganic Medicinal Chemistry 25 13 (2017): Pages 3259-3277.

[2] Stanley, S. “Chapter 150 – Antiparasitic agents.”Infectious Diseases (Third Edition) 2 (2010): 1490-1507.