Marked variation in pyrimethamine disposition in AIDS patients treated for cerebral toxoplasmosis.

Abstract

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.

• Authors: P Winstanley, S Khoo, S Szwandt, G Edwards, E Wilkins, J Tija, R Coker, W McKane, N Beeching, S Watkin
• Journal: The Journal of antimicrobial chemotherapy (J Antimicrob Chemother) Vol. 36 Issue 2 Pg. 435-9 (Aug 1995) ISSN: 0305-7453 [Print] England
• PMID: 8522475 (Publication Type: Clinical Trial, Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Anti-Infective Agents
• Pyrimethamine

Topics

• Acquired Immunodeficiency Syndrome (complications, metabolism)
• Adult
• Anti-Infective Agents (pharmacokinetics, therapeutic use)
• Female
• Humans
• Male
• Middle Aged
• Pyrimethamine (pharmacokinetics, therapeutic use)
• Toxoplasmosis, Cerebral (drug therapy, etiology, metabolism)