Drug monitoring of pyrimethamine during maintenance therapy of toxoplasmic encephalitis in patients with advanced HIV infection during HAART.

Background: Prophylaxis of toxoplasmic encephalitis was performed with pyrimethamine in 6 patients with advanced HIV infection during combination therapy with protease inhibitors.

Material/methods: Steady-state plasma pyrimethamine (PYR) levels were measured by gas chromatography. Protease inhibitor plasma concentrations were analyzed trough concentration by high pressure liquid chromatography. During a treatment period of 22I13 months a total of 93 samples from 6 patients were investigated, containing pyrimethamine and protease inhibitors.

Results: The mean pyrimethamine concentration was 1,108+/-459 ng/ml with a dosage of 37.5 mg/d and 1, 685+/-665 ng/ml with 50 mg/d. With the simultaneous use of indinavir (IDV), a mean pyrimethamine concentration of 2,165+/-273 ng/ml was found, significantly higher than in combination with saquinavir (SQV) and ritonavir (RTV) (1,192+/-178 ng/ml) or saquinavir and nelfinavir (NLV) (1,117+/-173 ng/ml). This effect was not considered clinically significant. Drug monitoring of protease inhibitors revealed a wide range of protease inhibitor levels.

Conclusions: The statistically significant lower PYR concentrations with the SQV + RTV or SQV + NLV comedication in comparison to comedication with IDV were not considered clinically significant. Therapeutic drug monitoring of PYR and PI plasma levels can be recommended in patients during therapy with both PYR and PI, especially during therapy with a double PI regimen.