Skip to main content
NCBI home page
Antimicrobial Agents and Chemotherapy logoLink to Antimicrobial Agents and Chemotherapy
. 1993 Feb;37(2):187–190. doi: 10.1128/aac.37.2.187

Uptake and intracellular activity of fluconazole in human polymorphonuclear leukocytes.

A Pascual 1, I García 1, C Conejo 1, E J Perea 1
PMCID: PMC187636  PMID: 8452347

Abstract

The penetration of fluconazole into human polymorphonuclear leukocytes (PMNs) and tissue culture epithelial cells (McCoy) was evaluated. At different extracellular concentrations (0.5 to 10 mg/liter), fluconazole reached cell-associated concentrations greater than the extracellular ones in either human PMNs (intracellular concentration to extracellular concentration ratio, > or = 2.2) or McCoy cells (intracellular concentration to extracellular concentration ratio, > or = 1.3). The uptake of fluconazole by PMNs was rapid and reversible but was not energy dependent. The intracellular penetration of fluconazole was not affected by environmental pH or temperature. Ingestion of opsonized zymosan and opsonized Candida albicans did not significantly increase the amount of PMN-associated fluconazole. At therapeutic extracellular concentrations, the intracellular activity of fluconazole against C. albicans in PMNs was significantly lower than that of amphotericin B. It was concluded that fluconazole reaches high intracellular concentrations within PMNs but shows moderate activity against intracellular C. albicans in vitro.

Full text

PDF
187

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. De Wit S., Weerts D., Goossens H., Clumeck N. Comparison of fluconazole and ketoconazole for oropharyngeal candidiasis in AIDS. Lancet. 1989 Apr 8;1(8641):746–748. doi: 10.1016/s0140-6736(89)92572-5. [DOI] [PubMed] [Google Scholar]
  2. Humphrey M. J., Jevons S., Tarbit M. H. Pharmacokinetic evaluation of UK-49,858, a metabolically stable triazole antifungal drug, in animals and humans. Antimicrob Agents Chemother. 1985 Nov;28(5):648–653. doi: 10.1128/aac.28.5.648. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Johnson E. M., Richardson M. D., Warnock D. W. Effect of imidazole antifungals on the development of germ tubes by strains of Candida albicans. J Antimicrob Chemother. 1983 Oct;12(4):303–316. doi: 10.1093/jac/12.4.303. [DOI] [PubMed] [Google Scholar]
  4. Klempner M. S., Styrt B. Clindamycin uptake by human neutrophils. J Infect Dis. 1981 Nov;144(5):472–479. doi: 10.1093/infdis/144.5.472. [DOI] [PubMed] [Google Scholar]
  5. Odds F. C., Webster C. E. Effects of azole antifungals in vitro on host/parasite interactions relevant to Candida infections. J Antimicrob Chemother. 1988 Oct;22(4):473–481. doi: 10.1093/jac/22.4.473. [DOI] [PubMed] [Google Scholar]
  6. Pascual A., Garcia I., Perea E. J. Fluorometric measurement of ofloxacin uptake by human polymorphonuclear leukocytes. Antimicrob Agents Chemother. 1989 May;33(5):653–656. doi: 10.1128/aac.33.5.653. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Pascual A., Tsukayama D., Kovarik J., Gekker G., Peterson P. Uptake and activity of rifapentine in human peritoneal macrophages and polymorphonuclear leukocytes. Eur J Clin Microbiol. 1987 Apr;6(2):152–157. doi: 10.1007/BF02018197. [DOI] [PubMed] [Google Scholar]
  8. Peterson P. K., Verhoef J., Schmeling D., Quie P. G. Kinetics of phagocytosis and bacterial killing by human polymorphonuclear leukocytes and monocytes. J Infect Dis. 1977 Oct;136(4):502–509. doi: 10.1093/infdis/136.4.502. [DOI] [PubMed] [Google Scholar]
  9. Rogers T. E., Galgiani J. N. Activity of fluconazole (UK 49,858) and ketoconazole against Candida albicans in vitro and in vivo. Antimicrob Agents Chemother. 1986 Sep;30(3):418–422. doi: 10.1128/aac.30.3.418. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Roilides E., Walsh T. J., Rubin M., Venzon D., Pizzo P. A. Effects of antifungal agents on the function of human neutrophils in vitro. Antimicrob Agents Chemother. 1990 Feb;34(2):196–201. doi: 10.1128/aac.34.2.196. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Sugar A. M., Saunders C. Oral fluconazole as suppressive therapy of disseminated cryptococcosis in patients with acquired immunodeficiency syndrome. Am J Med. 1988 Oct;85(4):481–489. doi: 10.1016/s0002-9343(88)80082-2. [DOI] [PubMed] [Google Scholar]
  12. Tulkens P. M. Intracellular distribution and activity of antibiotics. Eur J Clin Microbiol Infect Dis. 1991 Feb;10(2):100–106. doi: 10.1007/BF01964420. [DOI] [PubMed] [Google Scholar]
  13. Van 't Wout J. W., Meynaar I., Linde I., Poell R., Mattie H., Van Furth R. Effect of amphotericin B, fluconazole and itraconazole on intracellular Candida albicans and germ tube development in macrophages. J Antimicrob Chemother. 1990 May;25(5):803–811. doi: 10.1093/jac/25.5.803. [DOI] [PubMed] [Google Scholar]

Articles from Antimicrobial Agents and Chemotherapy are provided here courtesy of American Society for Microbiology (ASM)

RESOURCES