CLINICAL PHARMACOLOGY
Pyrimethamine is well absorbed with peak levels occurring between
2 to 6 hours following administration. It is eliminated slowly
and has a plasma half-life of approximately 96 hours.
Pyrimethamine is 87% bound to human plasma proteins.
Microbiology: Pyrimethamine is a folic acid antagonist and the
rationale for its therapeutic action is based on the
differential requirement between host and parasite for nucleic
acid precursors involved in growth. This activity is highly
selective against plasmodia and Toxoplasma gondii.
Pyrimethamine possesses blood schizonticidal and some
tissue schizonticidal activity against malaria parasites of
humans. However, the 4-amino-quinoline compounds are more
effective against the erythrocytic schizonts. It does not
destroy gametocytes, but arrests sporogony in the mosquito.
The action of pyrimethamine against Toxoplasma gondii is greatly
enhanced when used in conjunction with sulfonamides. This was
demonstrated by Eyles and Coleman1 in the treatment
of experimental toxoplasmosis in the mouse. Jacobs et
al2 demonstrated that combination of the
2 drugs effectively prevented the development of severe
uveitis in most rabbits following the inoculation of the
anterior chamber of the eye with toxoplasma.
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