PLASMA PYRIMETHAMINE CONCENTRATIONS DURING LONG-TERM TREATMENT FOR CEREBRAL TOXOPLASMOSIS IN PATIENTS WITH AIDS

Steady-state plasma pyrimethamine levels were measured by gas chromato graphy. The specimens were taken from 74 adults with advanced human im munodeficiency virus infection receiving pyrimethamine-containing drug s for prophylaxis or curative therapy of reactivated cerebral toxoplas mosis. During an overall treatment period of 1,049 months, 1,012 plasm a samples were investigated, Pyrimethamine concentrations could be eva luated in 904 plasma samples, The weekly dosage of pyrimethamine range d from 25 to 1,400 mg; one patient with severe diarrhea received 2,100 mg/week. Steady-state plasma pyrimethamine concentrations were achiev ed after 12 to 20 days. Pyrimethamine concentrations evidently increas ed with the weekly dosage given. Mean concentrations were 253 +/- 151 ng/ml with 50 mg of pyrimethamine per week, 471 +/- 214 ng/ml with 100 mg of pyrimethamine per week, 1,893 +/- 1,182 ng/ml with 350 mg of py rimethamine per week and 3,369 +/- 1,726 ng/ml with 1,050 mg of pyrime thamine per week, A widespread interpatient range was found for every dosage, With the simultaneous use of enzyme-inducing comedication, the plasma pyrimethamine levels decreased in several patients, Mild chron ic liver disease did not influence plasma pyrimethamine concentrations , To avoid ineffective therapy or severe side effects, monitoring of p yrimethamine could be useful in patients receiving enzyme-inducing com edications and in patients with severe diarrhea or poor compliance.