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Please use this identifier to cite or link to this item: http://repository.li.mahidol.ac.th/dspace/handle/123456789/29729
Title: Monitoring and impact of fluconazole serum and cerebrospinal fluid concentration in HIV-associated cryptococcal meningitis-infected patients
Authors: W. Manosuthi
P. Chetchotisakd
T. L. Nolen
D. Wallace
S. Sungkanuparph
T. Anekthananon
K. Supparatpinyo
P. G. Pappas
R. A. Larsen
S. G. Filler
D. Andes
Bamrasnaradura Infectious Diseases Institute
Khon Kaen University
Rho Federal Systems Division, Inc.
RTI International
Mahidol University
Faculty of Medicine, Chiang Mai University
University of Alabama School of Medicine
Keck School of Medicine of USC
David Geffen School of Medicine at UCLA
University of Wisconsin Madison
Keywords: Medicine
Issue Date: 1-Apr-2010
Citation: HIV Medicine. Vol.11, No.4 (2010), 276-281
Abstract: Objectives:The aim of the present study was to assess fluconazole pharmacokinetic measures in serum and cerebrospinal fluid (CSF); and the correlation of these measures with clinical outcomes of invasive fungal infections. Methods:A randomized trial was conducted in HIV-infected patients receiving three different regimens of fluconazole plus amphotericin B (AmB) for the treatment of cryptococcal meningitis. Regimens included fluconazole 400 mg/day+AmB (AmB+Fluc400) or fluconazole 800 mg/day+AmB (AmB+Fluc800) (14 days followed by fluconazole alone at the randomized dose for 56 days); or AmB alone for 14 days followed by fluconazole 400 mg/day for 56 days. Serum (at 24 h after dosing) and CSF samples were taken at baseline and days 14 and 70 (serum only) for fluconazole measurement, using gas-liquid chromatography. Results: Sixty-four treated patients had fluconazole measurements: 11 in the AmB group, 12 in the AmB+Fluc400 group and 41 in the AmB+Fluc800 group. Day 14 serum concentration geometric means were 24.7 mg/L for AmB+Fluc400 and 37.0 mg/L for AmB+Fluc800. Correspondingly, CSF concentration geometric means were 25.1 mg/L and 32.7 mg/L. Day 14 Serum and CSF concentrations were highly correlated with AmB+Fluc800 (P<0.001, r=0.873) and AmB+Fluc400 (P=0.005, r=0.943). Increased serum area under the curve (AUC) appears to be associated with decreased mortality at day 70 (P=0.061, odds ratio=2.19) as well as with increased study composite endpoint success at days 42 and 70 (P=0.081, odds ratio=2.25 and 0.058, 2.89, respectively). Conclusion:High fluconazole dosage (800 mg/day) for the treatment of HIV-associated cryptococcal meningitis was associated with high serum and CSF fluconazole concentration. Overall, high serum and CSF concentration appear to be associated with increased survival and primary composite endpoint success. © 2009 British HIV Association.
URI: https://www.scopus.com/inward/record.uri?partnerID=HzOxMe3b&scp=77950813660&origin=inward
http://repository.li.mahidol.ac.th/dspace/handle/123456789/29729
ISSN: 14681293
14642662
Appears in Collections:Scopus 2006-2010

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