Clinical Drug Investigation

, Volume 10, Issue 2, pp 104–109 | Cite as

Pharmacokinetics of Fluconazole in the Serum and Exudate of the Pelvic Retroperitoneal Space after Radical Hysterectomy and Pelvic Lymphadenectomy

  • Hiroshige Mikamo
  • Kyoko Kawazoe
  • Koji Izumi
  • Kunihiko Ito
  • Teruhiko Tamaya
Clinical Pharmacokinetics

Summary

The use of systemic antifungal agents has increased in recent years, partly as a result of the increasing incidence of compromised hosts. In gynaecology, the decision of which of these drugs to use has been a difficult one. The efficacies of these drugs depend on their antifungal spectra, potencies and tissue concentrations. This study investigated the pharmacokinetics of fluconazole in the serum and exudate of the retroperitoneal space that is formed after radical hysterectomy and pelvic lymphadenectomy. Fluconazole 200mg was administered to study patients for exactly 60 minutes using an automatic drip infusion pump. The parameters of the formulae analysed by the 2-compartment model were determined by the least-squares method, and a simulation curve was made. The maximum drug concentration (Cmax) of fluconazole in serum was 6.2 mg/L at 1.0 hour after beginning the drip infusion. The half-life of fluconazole in serum was very long, i.e. 17.7 hours after the start of the drip infusion. The area under the serum concentration-time curve (AUC) was 140.4 µg/ml·h. The Cmax of fluconazole in the exudate of the retroperitoneal space was 4.3 mg/L at 4.7 hours after the start of the drip infusion. The AUC in the exudate was 167.5 µg/ml·h. Fluconazole therefore appears to show considerable potential for attaining satisfactory tissue concentrations in the treatment of systemic fungal infections.

Keywords

Adis International Limited Fluconazole Antimicrob Agent Drug Invest Radical Hysterectomy 

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References

  1. 1.
    Cohen J. Treatment of systemic yeast infection with fluconazole. J Antimicrob Chemother 1989; 23: 294PubMedCrossRefGoogle Scholar
  2. 2.
    Conti DJ, Tolkoff-Rubin NE, Baker Jr GP, et al. Successful treatment of invasive fungal infection with fluconazole in organ transplant recipients. Transplantation 1989; 48: 692–4PubMedGoogle Scholar
  3. 3.
    Ikemoto H, Watanabe K, Mori T, et al. Clinical study of fluconazole on deep-seated fungal infections. Jpn J Antibiot 1989; 42: 63–116PubMedCrossRefGoogle Scholar
  4. 4.
    Nakashima M. The clinical study of fluconazole against pulmonary mycosis. Effects of fluconazole on pulmonary cryptococcosis and aspergillosis and its pharmacokinetics in patients. Jpn J Antibiot 1989; 42: 127–37PubMedCrossRefGoogle Scholar
  5. 5.
    Bodey GP. Infection in cancer patients. Am J Med 1986; 81Suppl. 1A: 11–26PubMedCrossRefGoogle Scholar
  6. 6.
    Humphrey MJ, Jevons S, Tarbit MH. Pharmacokinetic evaluation of UK-49858, a metabolically stable triazole antifungal drug, in animals and humans. Antimicrob Agents Chemother 1985; 28: 648–53PubMedCrossRefGoogle Scholar
  7. 7.
    Shiba K, Saito A, Miyahara T. Pharmacokinetic evaluation of fluconazole in healthy volunteers. Jpn J Antibiot 1989; 42: 17–30PubMedGoogle Scholar
  8. 8.
    Walsh TJ, Foulds G, Pizzo PA. Pharmacokinetics and tissue penetration of fluconazole in rabbits. Antimicrob Agents Chemother 1989; 33: 467–9PubMedCrossRefGoogle Scholar
  9. 9.
    Mizuta E, Tsubotani A. A pharmacokinetic model for stimulating drug concentrations in the tissue or fluids and its application to antibiotics. Chem Pharm Bull 1985; 33: 2974–82PubMedCrossRefGoogle Scholar
  10. 10.
    Bodey GP. Fungal infection and fever of unknown origin in neutropenic patients. Am J Med 1986; 80Suppl. 5C: 112–9PubMedGoogle Scholar
  11. 11.
    Bodey GP, Fainstein V. Systemic candidiasis. In: Bodey GP, Fainstein V, editors. Candidiasis. New York: Raven Press, 1985; 135–68Google Scholar
  12. 12.
    Van’t Wout JW, Mattie H, Van Furth R. Comparison of the efficacies of amphotericin B, fluconazole, and itraconazole against a systemic Candida albicans infection in normal and neutropenic mice. Antimicrob Agents Chemother 1989; 33: 147–51CrossRefGoogle Scholar
  13. 13.
    Yamaguchi H, Uchida K, Kawasaki K, et al. In vitro activity of fluconazole, a novel bistriazole antifungal agent. Jpn J Antibiot 1989; 42: 1–16PubMedCrossRefGoogle Scholar
  14. 14.
    Rogers TE, Galgiani JN. Activity of fluconazole (UK 49,858) and ketoconazole against Candida albicans in vitro and in vivo. Antimicrob Agents Chemother 1986; 30: 418–22PubMedCrossRefGoogle Scholar

Copyright information

© Adis International Limited 1995

Authors and Affiliations

  • Hiroshige Mikamo
    • 1
  • Kyoko Kawazoe
    • 1
  • Koji Izumi
    • 1
  • Kunihiko Ito
    • 1
  • Teruhiko Tamaya
    • 1
  1. 1.Department of Obstetrics and Gynecology, School of MedicineGifu UniversityGifu-City, GifuJapan

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