Clinical Pharmacokinetics

, Volume 43, Issue 11, pp 725–732 | Cite as

Effect of Rifampicin on the Pharmacokinetics of Fluconazole in Patients with AIDS

  • Duangchit Panomvana Na Ayudhya
  • Nawarat Thanompuangseree
  • Somsit Tansuphaswadikul
Original Research Article

Abstract

Objective

To study the effect of rifampicin on the pharmacokinetics of fluconazole and on clinical outcomes of fluconazole treatment in patients with AIDS-related cryptococcal meningitis.

Patients

Forty Thai patients with AIDS and cryptococcal meningitis, of whom 20 had been receiving oral rifampicin for at least 2 weeks to treat tuberculosis.

Methods

Patients were treated for cryptococcal meningitis with amphotericin 0.7 mg/kg/day for 14 days followed by fluconazole 400 mg/day, which was reduced to 200 mg/day once culture of cerebrospinal fluid (CSF) became negative. Patients with tuberculosis received oral rifampicin 600 mg/day at night. Blood samples were collected from the first 12 patients in each group and pharmacokinetic parameters for fluconazole were calculated. CSF samples were collected by lumbar puncture and monitored for eradication of Cryptococcus neoformans.

Results

Concomitant administration of rifampicin with fluconazole resulted in significant changes in the pharmacokinetic parameters of fluconazole, including a 39% increase in elimination rate constant, 28% shorter elimination half-life, 22% decrease in area under the concentration-time curve, 17% decrease in maximum concentration and 30% increase in clearance (p < 0.05). Different fluconazole regimens did not affect the extent of change in the elimination rate constant. Although serum concentrations of fluconazole during the time that patients received rifampicin concomitantly with fluconazole 200 mg/day were generally lower than the minimum inhibitory concentration for C. neoformans, there were no significant differences in clinical outcomes between the two groups to date (p = 0.792).

Conclusions

Coadministration of rifampicin with fluconazole caused significant changes in the pharmacokinetic parameters of fluconazole. Long-term monitoring for recurrence rates of cryptococcal meningitis is required to assess the clinical significance of this interaction.

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Copyright information

© Adis Data Information BV 2004

Authors and Affiliations

  • Duangchit Panomvana Na Ayudhya
    • 1
  • Nawarat Thanompuangseree
    • 2
  • Somsit Tansuphaswadikul
    • 3
  1. 1.Department of Clinical Pharmacy, Faculty of Pharmaceutical SciencesChulalongkorn UniversityBangkokThailand
  2. 2.Department of PharmacySuratthani HospitalSuratthaniThailand
  3. 3.Department of MedicineBamrajnaradura HospitalNonthaburiThailand

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