HOMEPRODUCTSCOMPANYCONTACTFAQResearchDictionaryPharmaSign Up FREE or Login

Oral versus intravenous flucytosine in patients with human immunodeficiency virus-associated cryptococcal meningitis.

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 cerebrospinal 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.
AuthorsAnnemarie E Brouwer, Hendrikus J M van Kan, Elizabeth Johnson, Adul Rajanuwong, Prapit Teparrukkul, Vannaporn Wuthiekanun, Wirongrong Chierakul, Nick Day, Thomas S Harrison
JournalAntimicrobial agents and chemotherapy (Antimicrob Agents Chemother) Vol. 51 Issue 3 Pg. 1038-42 (Mar 2007) ISSN: 0066-4804 [Print] United States
PMID17194824 (Publication Type: Comparative Study, Journal Article, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)
Chemical References
  • Antifungal Agents
  • Hemoglobins
  • Flucytosine
Topics
  • Administration, Oral
  • Adult
  • Antifungal Agents (administration & dosage, pharmacokinetics, therapeutic use)
  • Area Under Curve
  • Female
  • Flucytosine (administration & dosage, pharmacokinetics, therapeutic use)
  • HIV Infections (complications)
  • Hemoglobins (metabolism)
  • Humans
  • Injections, Intravenous
  • Male
  • Meningitis, Cryptococcal (drug therapy, etiology, microbiology)
  • Microbial Sensitivity Tests

Join CureHunter, for free Research Interface BASIC access!

Take advantage of free CureHunter research engine access to explore the best drug and treatment options for any disease. Find out why thousands of doctors, pharma researchers and patient activists around the world use CureHunter every day.
Realize the full power of the drug-disease research graph!


Choose Username:
Email:
Password:
Verify Password:
Enter Code Shown: