Plasma pyrimethamine concentrations during long-term treatment for cerebral toxoplasmosis in patients with AIDS.
Steady-state plasma pyrimethamine levels were measured by gas chromatography. The specimens were taken from 74 adults with advanced human immunodeficiency virus infection receiving pyrimethamine-containing drugs for prophylaxis or curative therapy of reactivated cerebral toxoplasmosis. During an overall treatment period of 1,049 months, 1,012 plasma samples were investigated. Pyrimethamine concentrations could be evaluated in 904 plasma samples. The weekly dosage of pyrimethamine ranged from 25 to 1,400 mg; one patient with severe diarrhea received 2,100 mg/week. Steady-state plasma pyrimethamine concentrations were achieved after 12 to 20 days. Pyrimethamine concentrations evidently increased 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 pyrimethamine per week and 3,369 +/- 1,726 ng/ml with 1,050 mg of pyrimethamine 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 chronic liver disease did not influence plasma pyrimethamine concentrations. To avoid ineffective therapy or severe side effects, monitoring of pyrimethamine could be useful in patients receiving enzyme-inducing comedications and in patients with severe diarrhea or poor compliance.
Klinker
H
H
Department of Internal Medicine, University of Würzburg, Germany.
Langmann
P
P
Richter
E
E
D017088:AIDS-Related Opportunistic Infections / Q000097:blood* / Q000188:drug therapy*; D004305:Dose-Response Relationship, Drug; D004660:Encephalitis / Q000097:blood* / Q000188:drug therapy*; D006801:Humans; D011739:Pyrimethamine / Q000097:blood* / Q000627:therapeutic use*; D016781:Toxoplasmosis, Cerebral / Q000097:blood* / Q000188:drug therapy*
D011739:Pyrimethamine