Indications
Pyrimethamine is indicated for the treatment of toxoplasmosis and acute malaria. It is also used for the prevention of malaria in regions where the malaria parasite has not developed resistance to pyrimethamine. By targeting specific stages of the parasite lifecycle, pyrimethamine effectively contributes to malaria management strategies, especially in non-resistant areas.
Pharmacodynamics
Pyrimethamine acts as an antiparasitic agent, primarily serving as an adjunct treatment for uncomplicated cases of chloroquine-resistant Plasmodium falciparum malaria. As a folic acid antagonist, its effectiveness arises from exploiting the differences in nucleic acid precursor requirements between the host and the parasite. Its selective activity is particularly potent against the plasmodia and Toxoplasma gondii. While pyrimethamine displays blood schizonticidal and limited tissue schizonticidal activity, it is less effective against erythrocytic schizonts compared to the 4-amino-quinoline compounds. Though it does not eliminate gametocytes, pyrimethamine inhibits sporogony within the mosquito vector. When used alongside sulfonamides, its efficacy against Toxoplasma gondii is significantly increased.
Absorption
Pyrimethamine is well absorbed following administration, with peak plasma concentrations typically achieved between 2 to 6 hours. This pharmacokinetic profile supports its use in consistent therapeutic regimens, allowing for predictable drug availability in the system.
Metabolism
Pyrimethamine undergoes metabolic processing primarily in the liver. This hepatic metabolism plays a crucial role in the drug's efficacy and safety profile, ensuring its therapeutic effectiveness while minimizing potential toxicity through biotransformation.
Mechanism of Action
Pyrimethamine functions by inhibiting the dihydrofolate reductase enzyme in plasmodium species, effectively halting the biosynthesis of purines and pyrimidines. These nucleic acids are critical for DNA synthesis and cell proliferation. As a consequence, nuclear division is disrupted during schizont formation within erythrocytes and the liver, impeding the life cycle of the parasite.
