PYRIMETHAMINE PHARMACOKINETICS IN HUMAN IMMUNODEFICIENCY VIRUS-POSITIVE PATIENTS SEROPOSITIVE FOR TOXOPLASMA-GONDII

Pyrimethamine pharmacokinetics were studied in 11 human immunodeficien cy virus (HIV)-positive patients who were seropositive for exposure to Toxoplasma gondii and were taking zidovudine (AIDS Clinical Trials Gr oup Protocol 102), Pyrimethamine was administered at 50 mg daily for 3 weeks to achieve steady state, and pharmacokinetic profiles were dete rmined after administration of the last dose, Noncompartmental and com partmental analyses were performed. Population pharmacokinetic analysi s assuming a one-compartment model yielded the following estimates: ar ea under the 24-h concentration-time curve, 42.7 +/- 12.3 mu g . h/ml; half-life, 139 +/- 34 h; clearance, 1.28 +/- 0.41 liters/h; volume of distribution, 246 +/- 641; and absorption rate constant, 1.5 +/- 1.3 liters/h. These values are similar to those seen in subjects without H IV infection, Pyrimethamine pharmacokinetics did not differ significan tly in those subjects who were intravenous drug users. Adverse effects were noted in 73% of those initially enrolled in this study, leading to discontinuation for 38%. No association was noted between pyrimetha mine levels and the incidence of adverse events. No significant differ ences were seen in zidovudine pharmacokinetic parameters obtained from studies performed before and during treatment with pyrimethamine. In summary, pyrimethamine exhibited pharmacokinetics in HIV-infected pati ents that were similar to those in non-HIV-infected subjects and it di d not alter the pharmacokinetics of zidovudine in these patients.