P02: Anthelmintics
P02 holds the anthelmintics: drugs against flukes (antitrematodals, P02B), roundworms (antinematodal agents, P02C) and tapeworms (anticestodals, P02D) [1].
How do they work?
Many anthelmintics were first found by screening compounds against worms, without a known target, and only later found to act on ion channels. Praziquantel (P02BA01) is the current treatment for infection with flatworms that live in the blood (schistosomiasis). It activates a transient receptor potential (TRP) channel of the parasite, causing a massive and persistent influx of calcium. The worms are paralyzed and their outer surface (tegument) is damaged, which triggers detection by the host immune system and clearance of the parasites. Among the drugs against roundworms, ivermectin (P02CF01) acts on a different kind of ion channel, the glutamate-gated chloride channels [2].
Efficacy
In trials against worms spread through soil (soil-transmitted helminths), anthelmintic efficacy is expressed as the cure rate, the percentage of patients whose stools become free of eggs, and the egg reduction rate [3].
For tribendimidine against hookworm in children and adolescents, Emax models linked exposure to its active metabolite with the cure rate and the egg reduction rate. The curves were shallow: a 12-fold higher dose would have been needed to reach an egg reduction rate of 95% and a cure rate above 90%, so the authors suggested combination therapy. The tribendimidine pharmacokinetic model included allometric scaling to account for growth and development [4].