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. 1997 May;41(5):914–917. doi: 10.1128/aac.41.5.914

Pharmacokinetics of oral fluconazole when used for prophylaxis in bone marrow transplant recipients.

A El-Yazigi 1, M Ellis 1, P Ernst 1, D Spence 1, R Hussain 1, F J Baillie 1
PMCID: PMC163824  PMID: 9145843

Abstract

The pharmacokinetics of fluconazole was investigated in 20 bone marrow transplant patients following oral administration of 200 mg of this drug. Blood samples were collected from each patient at different time intervals within 48 h after the first dose, and fluconazole was measured in plasma by high-performance liquid chromatography with UV detection. Urine was collected from 14 of these patients and analyzed similarly. The plasma concentration-time data exhibited the characteristics of the one-compartment model with first-order absorption quite well. The means +/- standard deviations of half-lives for absorption and elimination, peak concentration, time to peak, mean residence time, apparent volumes of distribution, area under the curve, and apparent oral clearance observed in these patients were 2.84 +/- 1.34 h, 19.94 +/- 18.7 h, 4.45 +/- 1.86 microg/ml, 8.34 +/- 5.97 h, 39.57 +/- 20.5 h, 0.874 +/- 0.48 liter/kg, 156.0 +/- 60.6 microg x h/ml, and 0.0256 +/- 0.0138 liter/h x kg, respectively. The amount of fluconazole excreted in urine in 24 h was 67.1 +/- 83 mg, which represents 33.55% +/- 41.6% of the dose administered. Patients who developed hemorrhagic cystitis excreted significantly (P < or = 0.0094) more fluconazole in 24 h than did those who did not.

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Selected References

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  1. Brammer K. W., Coates P. E. Pharmacokinetics of fluconazole in pediatric patients. Eur J Clin Microbiol Infect Dis. 1994 Apr;13(4):325–329. doi: 10.1007/BF01974613. [DOI] [PubMed] [Google Scholar]
  2. DeMuria D., Forrest A., Rich J., Scavone J. M., Cohen L. G., Kazanjian P. H. Pharmacokinetics and bioavailability of fluconazole in patients with AIDS. Antimicrob Agents Chemother. 1993 Oct;37(10):2187–2192. doi: 10.1128/aac.37.10.2187. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Efros M. D., Ahmed T., Coombe N., Choudhury M. S. Urologic complications of high-dose chemotherapy and bone marrow transplantation. Urology. 1994 Mar;43(3):355–360. doi: 10.1016/0090-4295(94)90079-5. [DOI] [PubMed] [Google Scholar]
  4. Ellis M. E., Clink H., Ernst P., Halim M. A., Padmos A., Spence D., Kalin M., Hussain Qadri S. M., Burnie J., Greer W. Controlled study of fluconazole in the prevention of fungal infections in neutropenic patients with haematological malignancies and bone marrow transplant recipients. Eur J Clin Microbiol Infect Dis. 1994 Jan;13(1):3–11. doi: 10.1007/BF02026116. [DOI] [PubMed] [Google Scholar]
  5. Fischman A. J., Alpert N. M., Livni E., Ray S., Sinclair I., Callahan R. J., Correia J. A., Webb D., Strauss H. W., Rubin R. H. Pharmacokinetics of 18F-labeled fluconazole in healthy human subjects by positron emission tomography. Antimicrob Agents Chemother. 1993 Jun;37(6):1270–1277. doi: 10.1128/aac.37.6.1270. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Goodman J. L., Winston D. J., Greenfield R. A., Chandrasekar P. H., Fox B., Kaizer H., Shadduck R. K., Shea T. C., Stiff P., Friedman D. J. A controlled trial of fluconazole to prevent fungal infections in patients undergoing bone marrow transplantation. N Engl J Med. 1992 Mar 26;326(13):845–851. doi: 10.1056/NEJM199203263261301. [DOI] [PubMed] [Google Scholar]
  7. Inagaki K., Takagi J., Lor E., Okamoto M. P., Gill M. A. Determination of fluconazole in human serum by solid-phase extraction and reversed-phase high-performance liquid chromatography. Ther Drug Monit. 1992 Aug;14(4):306–311. doi: 10.1097/00007691-199208000-00008. [DOI] [PubMed] [Google Scholar]
  8. Krzeska I., Yeates R. A., Pfaff G. Single dose intravenous pharmacokinetics of fluconazole in infants. Drugs Exp Clin Res. 1993;19(6):267–271. [PubMed] [Google Scholar]
  9. Lee J. W., Seibel N. L., Amantea M., Whitcomb P., Pizzo P. A., Walsh T. J. Safety and pharmacokinetics of fluconazole in children with neoplastic diseases. J Pediatr. 1992 Jun;120(6):987–993. doi: 10.1016/s0022-3476(05)81975-4. [DOI] [PubMed] [Google Scholar]
  10. McLachlan A. J., Tett S. E. Pharmacokinetics of fluconazole in people with HIV infection: a population analysis. Br J Clin Pharmacol. 1996 Apr;41(4):291–298. doi: 10.1046/j.1365-2125.1996.03085.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Milliken S., Powles R., Jones A., Helenglass G. Pharmacokinetics of oral fluconazole in autologous bone marrow transplantation recipients given TBI and high-dose melphalan. Transplant Proc. 1989 Feb;21(1 Pt 3):3067–3067. [PubMed] [Google Scholar]
  12. Ripa S., Ferrante L., Prenna M. Pharmacokinetics of fluconazole in normal volunteers. Chemotherapy. 1993;39(1):6–12. doi: 10.1159/000238967. [DOI] [PubMed] [Google Scholar]
  13. Ruhnke M., Yeates R. A., Pfaff G., Sarnow E., Hartmann A., Trautmann M. Single-dose pharmacokinetics of fluconazole in patients with liver cirrhosis. J Antimicrob Chemother. 1995 May;35(5):641–647. doi: 10.1093/jac/35.5.641. [DOI] [PubMed] [Google Scholar]
  14. Sculier J. P., Weerts D., Klastersky J. Causes of death in febrile granulocytopenic cancer patients receiving empiric antibiotic therapy. Eur J Cancer Clin Oncol. 1984 Jan;20(1):55–60. doi: 10.1016/0277-5379(84)90034-8. [DOI] [PubMed] [Google Scholar]
  15. Seay R. E., Larson T. A., Toscano J. P., Bostrom B. C., O'Leary M. C., Uden D. L. Pharmacokinetics of fluconazole in immune-compromised children with leukemia or other hematologic diseases. Pharmacotherapy. 1995 Jan-Feb;15(1):52–58. [PubMed] [Google Scholar]
  16. Shiba K., Saito A., Miyahara T. Safety and pharmacokinetics of single oral and intravenous doses of fluconazole in healthy subjects. Clin Ther. 1990 May-Jun;12(3):206–215. [PubMed] [Google Scholar]
  17. Tett S., Moore S., Ray J. Pharmacokinetics and bioavailability of fluconazole in two groups of males with human immunodeficiency virus (HIV) infection compared with those in a group of males without HIV infection. Antimicrob Agents Chemother. 1995 Aug;39(8):1835–1841. doi: 10.1128/aac.39.8.1835. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Thorpe J. E., Baker N., Bromet-Petit M. Effect of oral antacid administration on the pharmacokinetics of oral fluconazole. Antimicrob Agents Chemother. 1990 Oct;34(10):2032–2033. doi: 10.1128/aac.34.10.2032. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Toon S., Ross C. E., Gokal R., Rowland M. An assessment of the effects of impaired renal function and haemodialysis on the pharmacokinetics of fluconazole. Br J Clin Pharmacol. 1990 Feb;29(2):221–226. doi: 10.1111/j.1365-2125.1990.tb03623.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Wingard J. R., Merz W. G., Rinaldi M. G., Johnson T. R., Karp J. E., Saral R. Increase in Candida krusei infection among patients with bone marrow transplantation and neutropenia treated prophylactically with fluconazole. N Engl J Med. 1991 Oct 31;325(18):1274–1277. doi: 10.1056/NEJM199110313251803. [DOI] [PubMed] [Google Scholar]
  21. Winston D. J., Chandrasekar P. H., Lazarus H. M., Goodman J. L., Silber J. L., Horowitz H., Shadduck R. K., Rosenfeld C. S., Ho W. G., Islam M. Z. Fluconazole prophylaxis of fungal infections in patients with acute leukemia. Results of a randomized placebo-controlled, double-blind, multicenter trial. Ann Intern Med. 1993 Apr 1;118(7):495–503. doi: 10.7326/0003-4819-118-7-199304010-00003. [DOI] [PubMed] [Google Scholar]
  22. Yeates R. A., Ruhnke M., Pfaff G., Hartmann A., Trautmann M., Sarnow E. The pharmacokinetics of fluconazole after a single intravenous dose in AIDS patients. Br J Clin Pharmacol. 1994 Jul;38(1):77–79. doi: 10.1111/j.1365-2125.1994.tb04325.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Zimmermann T., Yeates R. A., Laufen H., Pfaff G., Wildfeuer A. Influence of concomitant food intake on the oral absorption of two triazole antifungal agents, itraconazole and fluconazole. Eur J Clin Pharmacol. 1994;46(2):147–150. doi: 10.1007/BF00199879. [DOI] [PubMed] [Google Scholar]
  24. Zimmermann T., Yeates R. A., Riedel K. D., Lach P., Laufen H. The influence of gastric pH on the pharmacokinetics of fluconazole: the effect of omeprazole. Int J Clin Pharmacol Ther. 1994 Sep;32(9):491–496. [PubMed] [Google Scholar]

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