Abstract
A simplified high-performance liquid chromatography assay was developed for determination of itraconazole levels in plasma and esophageal tissue in four patients with AIDS who had been receiving daily oral doses of 100 mg of itraconazole in solution for at least 3 weeks for therapy of esophageal candidiasis. Itraconazole levels were about three times higher in esophageal tissue than in plasma (means +/- standard errors of 0.69 +/- 0.50 micrograms/g and 0.24 +/- 0.16 micrograms/ml, respectively; P = 0.04). This method is quick (it requires only 1 h for completion) and sensitive (the limits of detectability for itraconazole in plasma and esophageal tissue are 0.005 micrograms/ml and 0.01 micrograms/g, respectively), and it can be reliably used in clinical and research settings (accuracy, > 95%; absolute recovery from biological samples, 80 to 90%; coefficient of variation, 3.3 to 6.6%).
Full Text
The Full Text of this article is available as a PDF (166.7 KB).
Selected References
These references are in PubMed. This may not be the complete list of references from this article.
- Akova M., Akalin H. E., Uzun O., Hayran M., Tekuzman G., Kansu E., Aslan S., Telatar H. Efficacy of fluconazole in the treatment of upper gastrointestinal candidiasis in neutropenic patients with cancer: factors influencing the outcome. Clin Infect Dis. 1994 Mar;18(3):298–304. doi: 10.1093/clinids/18.3.298. [DOI] [PubMed] [Google Scholar]
- Barone J. A., Koh J. G., Bierman R. H., Colaizzi J. L., Swanson K. A., Gaffar M. C., Moskovitz B. L., Mechlinski W., Van de Velde V. Food interaction and steady-state pharmacokinetics of itraconazole capsules in healthy male volunteers. Antimicrob Agents Chemother. 1993 Apr;37(4):778–784. doi: 10.1128/aac.37.4.778. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Berenguer J., Ali N. M., Allende M. C., Lee J., Garrett K., Battaglia S., Piscitelli S. C., Rinaldi M. G., Pizzo P. A., Walsh T. J. Itraconazole for experimental pulmonary aspergillosis: comparison with amphotericin B, interaction with cyclosporin A, and correlation between therapeutic response and itraconazole concentrations in plasma. Antimicrob Agents Chemother. 1994 Jun;38(6):1303–1308. doi: 10.1128/aac.38.6.1303. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Cauwenbergh G., Degreef H., Heykants J., Woestenborghs R., Van Rooy P., Haeverans K. Pharmacokinetic profile of orally administered itraconazole in human skin. J Am Acad Dermatol. 1988 Feb;18(2 Pt 1):263–268. doi: 10.1016/s0190-9622(88)70037-7. [DOI] [PubMed] [Google Scholar]
- Como J. A., Dismukes W. E. Oral azole drugs as systemic antifungal therapy. N Engl J Med. 1994 Jan 27;330(4):263–272. doi: 10.1056/NEJM199401273300407. [DOI] [PubMed] [Google Scholar]
- Dupont B., Drouhet E. Early experience with itraconazole in vitro and in patients: pharmacokinetic studies and clinical results. Rev Infect Dis. 1987 Jan-Feb;9 (Suppl 1):S71–S76. doi: 10.1093/clinids/9.supplement_1.s71. [DOI] [PubMed] [Google Scholar]
- Hardin T. C., Graybill J. R., Fetchick R., Woestenborghs R., Rinaldi M. G., Kuhn J. G. Pharmacokinetics of itraconazole following oral administration to normal volunteers. Antimicrob Agents Chemother. 1988 Sep;32(9):1310–1313. doi: 10.1128/aac.32.9.1310. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Heykants J., Van Peer A., Van de Velde V., Van Rooy P., Meuldermans W., Lavrijsen K., Woestenborghs R., Van Cutsem J., Cauwenbergh G. The clinical pharmacokinetics of itraconazole: an overview. Mycoses. 1989;32 (Suppl 1):67–87. doi: 10.1111/j.1439-0507.1989.tb02296.x. [DOI] [PubMed] [Google Scholar]
- Hostetler J. S., Heykants J., Clemons K. V., Woestenborghs R., Hanson L. H., Stevens D. A. Discrepancies in bioassay and chromatography determinations explained by metabolism of itraconazole to hydroxyitraconazole: studies of interpatient variations in concentrations. Antimicrob Agents Chemother. 1993 Oct;37(10):2224–2227. doi: 10.1128/aac.37.10.2224. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Laine L., Dretler R. H., Conteas C. N., Tuazon C., Koster F. M., Sattler F., Squires K., Islam M. Z. Fluconazole compared with ketoconazole for the treatment of Candida esophagitis in AIDS. A randomized trial. Ann Intern Med. 1992 Oct 15;117(8):655–660. doi: 10.7326/0003-4819-117-8-655. [DOI] [PubMed] [Google Scholar]
- Pape J. W. Treatment of gastrointestinal infections. AIDS. 1988;2 (Suppl 1):S161–S167. doi: 10.1097/00002030-198800001-00024. [DOI] [PubMed] [Google Scholar]
- Perfect J. R., Savani D. V., Durack D. T. Comparison of itraconazole and fluconazole in treatment of cryptococcal meningitis and candida pyelonephritis in rabbits. Antimicrob Agents Chemother. 1986 Apr;29(4):579–583. doi: 10.1128/aac.29.4.579. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Saag M. S., Dismukes W. E. Azole antifungal agents: emphasis on new triazoles. Antimicrob Agents Chemother. 1988 Jan;32(1):1–8. doi: 10.1128/aac.32.1.1. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Selik R. M., Starcher E. T., Curran J. W. Opportunistic diseases reported in AIDS patients: frequencies, associations, and trends. AIDS. 1987 Sep;1(3):175–182. [PubMed] [Google Scholar]
- Smith D., van de Velde V., Woestenborghs R., Gazzard B. G. The pharmacokinetics of oral itraconazole in AIDS patients. J Pharm Pharmacol. 1992 Jul;44(7):618–619. doi: 10.1111/j.2042-7158.1992.tb05478.x. [DOI] [PubMed] [Google Scholar]
- Tricot G., Joosten E., Boogaerts M. A., Vande Pitte J., Cauwenbergh G. Ketoconazole vs. itraconazole for antifungal prophylaxis in patients with severe granulocytopenia: preliminary results of two nonrandomized studies. Rev Infect Dis. 1987 Jan-Feb;9 (Suppl 1):S94–S99. doi: 10.1093/clinids/9.supplement_1.s94. [DOI] [PubMed] [Google Scholar]
- Van Cutsem J., Van Gerven F., Janssen P. A. Activity of orally, topically, and parenterally administered itraconazole in the treatment of superficial and deep mycoses: animal models. Rev Infect Dis. 1987 Jan-Feb;9 (Suppl 1):S15–S32. doi: 10.1093/clinids/9.supplement_1.s15. [DOI] [PubMed] [Google Scholar]
- Van Peer A., Woestenborghs R., Heykants J., Gasparini R., Gauwenbergh G. The effects of food and dose on the oral systemic availability of itraconazole in healthy subjects. Eur J Clin Pharmacol. 1989;36(4):423–426. doi: 10.1007/BF00558308. [DOI] [PubMed] [Google Scholar]
- Warnock D. W., Turner A., Burke J. Comparison of high performance liquid chromatographic and microbiological methods for determination of itraconazole. J Antimicrob Chemother. 1988 Jan;21(1):93–100. doi: 10.1093/jac/21.1.93. [DOI] [PubMed] [Google Scholar]
- Woestenborghs R., Lorreyne W., Heykants J. Determination of itraconazole in plasma and animal tissues by high-performance liquid chromatography. J Chromatogr. 1987 Jan 23;413:332–337. doi: 10.1016/0378-4347(87)80249-9. [DOI] [PubMed] [Google Scholar]