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Please use this identifier to cite or link to this item: http://repository.li.mahidol.ac.th/dspace/handle/123456789/24983
Title: Oral versus intravenous flucytosine in patients with human immunodeficiency virus-associated cryptococcal meningitis
Authors: Annemarie E. Brouwer
Hendrikus J M Van Kan
Elizabeth Johnson
Adul Rajanuwong
Prapit Teparrukkul
Vannaporn Wuthiekanun
Wirongrong Chierakul
Nick Day
Thomas S. Harrison
St George's University of London
Mahidol University
Radboud University Nijmegen Medical Centre
Academic Medical Centre, University of Amsterdam
Health Protection Agency
Sappasitthiprasong Hospital
Nuffield Department of Clinical Medicine
Keywords: Medicine
Issue Date: 1-Mar-2007
Citation: Antimicrobial Agents and Chemotherapy. Vol.51, No.3 (2007), 1038-1042
Abstract: In a randomized controlled trial of amphotericin B-based therapy for human immunodeficiency virus (HIV)-associated cryptococcal meningitis in Thailand, we also compared the mycological efficacy, toxicity, and pharmacokinetics of oral versus intravenous flucytosine at 100 mg/kg of body weight/day for the initial 2 weeks. Half of 32 patients assigned to the two arms containing flucytosine were randomized to oral and half to intravenous flucytosine. Early fungicidal activity was determined from serial quantitative cultures of cerebro-spinal fluid (CSF), and toxicity was assessed by clinical and laboratory monitoring. Flucytosine and fluorouracil concentrations in plasma and CSF were measured by high-performance liquid chromatography. No significant bone marrow or hepatotoxicity was seen, there was no detectable difference in bone marrow toxicity between patients on intravenous and those on oral formulation, and no patients discontinued treatment. In patients receiving intravenous flucytosine, the median 24-h area under the concentration-time curve was significantly higher than in the oral group. Despite this difference, there was no difference in early fungicidal activity between patients on intravenous compared with patients on oral flucytosine. The results suggest that either formulation can be used safely at this dosage in a developing country setting, without drug concentration monitoring. The bioavailability of the oral formulation may be reduced in late-stage HIV-infected patients in Thailand. Concentrations of flucytosine with intravenous formulation at 100 mg/kg/day may be in excess of those required for maximal fungicidal activity. Copyright © 2007, American Society for Microbiology. All Rights Reserved.
URI: https://www.scopus.com/inward/record.uri?partnerID=HzOxMe3b&scp=33847679441&origin=inward
http://repository.li.mahidol.ac.th/dspace/handle/123456789/24983
ISSN: 00664804
Appears in Collections:Scopus 2006-2010

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