Encephalitis caused by Toxoplasma gondii has emerged as the most frequent cause of focal central nervous system infection in patients with AIDS. Untreated, the encephalitis is fatal. The best treatment for this disease has not been determined. Presently it is standard practice to administer a combination of pyrimethamine and sulfadiazine. Little is known about the pharmacokinetics of pyrimethamine in patients with AIDS receiving AZT. Furthermore, there are reports that patients already exposed to toxoplasmosis may not have uniform absorption of pyrimethamine.~Patients receive the study treatment for a total of 22 days. Patients are given an initial dose of pyrimethamine followed by a lower dose given as a single oral daily dose for 21 days. Patients continue to receive AZT at the dose prescribed prior to enrollment in the study. Patients receive leucovorin calcium once a day. Neither the leucovorin calcium nor the AZT are provided through the study.
To determine the manner in which pyrimethamine is metabolized and excreted in patients currently receiving zidovudine (AZT). An important goal of this measurement is to establish the optimal dose of pyrimethamine necessary to prevent the development of toxoplasmosis in AIDS patients or delay the subsequent return of toxoplasmic encephalitis.~Encephalitis caused by Toxoplasma gondii has emerged as the most frequent cause of focal central nervous system infection in patients with AIDS. Untreated, the encephalitis is fatal. The best treatment for this disease has not been determined. Presently it is standard practice to administer a combination of pyrimethamine and sulfadiazine. Little is known about the pharmacokinetics of pyrimethamine in patients with AIDS receiving AZT. Furthermore, there are reports that patients already exposed to toxoplasmosis may not have uniform absorption of pyrimethamine.