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

Peter Winstanley; Saye Khoo; Simon Szwandt; Geoffrey Edwards; Edmund Wilkins; John Tija; Richard Coker; William Mckane; Nicholas Beeching; Simon Watkin; Alasdair Breckenridge

doi:10.1093/jac/36.2.435

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

Peter Winstanley, Saye Khoo, Simon Szwandt, Geoffrey Edwards, Edmund Wilkins, John Tija, Richard Coker, William Mckane, Nicholas Beeching, Simon Watkin, Alasdair Breckenridge

Research output: Contribution to journal › Article › peer-review

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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.

Original language	English
Pages (from-to)	435-439
Number of pages	5
Journal	The Journal of Antimicrobial Chemotherapy
Volume	36
Issue number	2
DOIs	https://doi.org/10.1093/jac/36.2.435
Publication status	Published - 1 Aug 1995
Externally published	Yes

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title = "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.",

author = "Peter Winstanley and Saye Khoo and Simon Szwandt and Geoffrey Edwards and Edmund Wilkins and John Tija and Richard Coker and William Mckane and Nicholas Beeching and Simon Watkin and Alasdair Breckenridge",

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T1 - Marked variation in pyrimethamine disposition in AIDS patients treated for cerebral toxoplasmosis

AU - Winstanley, Peter

AU - Khoo, Saye

AU - Szwandt, Simon

AU - Edwards, Geoffrey

AU - Wilkins, Edmund

AU - Tija, John

AU - Coker, Richard

AU - Mckane, William

AU - Beeching, Nicholas

AU - Watkin, Simon

AU - Breckenridge, Alasdair

PY - 1995/8/1

Y1 - 1995/8/1

N2 - 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.

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.

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DO - 10.1093/jac/36.2.435

M3 - Article

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SP - 435

EP - 439

JO - The Journal of Antimicrobial Chemotherapy

JF - The Journal of Antimicrobial Chemotherapy

IS - 2

ER -

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

Abstract

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