       Document 0146
 DOCN  M9630146
 TI    Marked variation in pyrimethamine disposition in AIDS patients treated
       for cerebral toxoplasmosis.
 DT    9603
 AU    Winstanley P; Khoo S; Szwandt S; Edwards G; Wilkins E; Tija J; Coker R;
       McKane W; Beeching N; Watkin S; et al; Department of Pharmacology and
       Therapeutics, University of; Liverpool, UK.
 SO    J Antimicrob Chemother. 1995 Aug;36(2):435-9. Unique Identifier :
       AIDSLINE MED/96052030
 AB    We have characterized the disposition of pyrimethamine in 20 adults with
       advanced AIDS. After the first dose, the area under concentration versus
       time curves (corrected for dose-size) varied 13-fold. This marked
       variation in drug levels was also noted during accumulation towards
       steady-state: pyrimethamine levels were consistently below the suggested
       lower end of the therapeutic range (750 mg/L) in three severely ill
       patients with perturbed consciousness (two of whom received the drug by
       nasogastric tube). Possible mechanisms for these observations are
       discussed. Pyrimethamine levels may be an important determinant of the
       rate of response to treatment by AIDS patients with toxoplasmosis:
       therapeutic drug monitoring may have a role.
 DE    Acquired Immunodeficiency Syndrome/*COMPLICATIONS/*METABOLISM  Adult
       Anti-Infective Agents/*PHARMACOKINETICS/THERAPEUTIC USE  Female  Human
       Male  Middle Age  Pyrimethamine/*PHARMACOKINETICS/THERAPEUTIC USE
       Support, Non-U.S. Gov't  Toxoplasmosis, Cerebral/DRUG
       THERAPY/ETIOLOGY/*METABOLISM  CLINICAL TRIAL  JOURNAL ARTICLE

       SOURCE: National Library of Medicine.  NOTICE: This material may be
       protected by Copyright Law (Title 17, U.S.Code).

