• Prodrug
• Converted to active tizoxanide by ester cleavage, which is then reduced to an active intermediate
• Inhibits the enzyme pyruvate: ferredoxin oxidoreductase and disrupts the bioenergetics of the microorganism

• Prodrug
• Hydrolyzed to diloxanide
• Has the same MOA of 
• Metabolism via glucuronidation

• Antimalarial Drug
• Inhibits the mitochondrial respiratory chain
• Ubiquinone Reductase Inhibitor

• Poorly absorbed (increased with meals) -- very lipophilic drug
• Highly bound to plasma proteins
• Not significantly metabolized

• Antimalarial
• Same MOA as trimethoprim (DHFR inhibitor)

• Benzamidazole
• Inhibition of the enzyme fumarate reductase (disruption of the production of ATP)

• Poorly absorbed from GI
• Metabolized by CYP450 -- glucuronidation

• Poorly absorbed from GI
• Metabolized by CYP450 -- glucuronidation

• Benzamidazole
• Inhibition of the enzyme fumarate reductase (disruption of the production of ATP)

• Benzamidazole
• Inhibition of the enzyme fumarate reductase (disruption of the production of ATP)

• Poorly absorbed from GI
• Metabolized by CYP450 -- glucuronidation

Two Hypotheses

1.  IVM acts as either a GABA agonist (binds irreversibly to glutamate-gated chloride channels -- results in rapid decrease of microfilarial concentrations) or as an Inducer of Chloride Ion Influx, leading to hyperpolarization and muscle paralysis --> motility of microfalaria is reduced, which allows cytotoxic cells of the host to adhere to the parasite and parasite is eliminated

2.  Degeneration of microfilariae --> fewer microfilariae released from the female worms --> prevents further fertilization and production of microfilariae

More than one mechanism

• Ca2+ redistribution --> leads to muscle contraction and paralysis --> worm expulsion
• Inhibits phosphoinositide metabolism --> leads to the worm paralysis
• Affects glycogen content and energy metabolism

• Rapidly absorbed
• Metabolized (hydroxylation -- NOT on the aromatic ring)

• Oxamniquine must be metabolically activated by the addition of an ester group to the hydroxy group of the aromatic ring --> the ester is removed and the drug now has a positive charge
• After obtaining the positive charge, it becomes an intercalating agent that intercalates itself into the DNA

• The ester prodrug is metabolized to diloxanide -- results in an OH (polar handle) on the aromatic ring
• The polar handle is then glucuronidated