• Omar H. El-garhy Department Department of Pharmaceutics, Faculty of Pharmacy, Minia University, Minia, Egypt


Human fungal infections, Azoles of interest, Different characteristics and development in the antifungal chemotherapy


In the last years, the risk of human fungal infections has been extensively increased with the increasing immune suppressed patients. Fortunately, the therapy of fungal infections has been undergone an explosive period of development. It was found that the use of currently available azoles in combination with other antifungals is likely to provide enhanced efficacy. But, several factors lead to therapeutic failure or relapse after the antifungal therapy. These factors are concerned with the different characteristics of the antifungal (s) used. Thus, specialists should be carefully investigated the different characteristics of antifungals to avoid these factors and further to use the antifungals optimally.

The present review discussed the different characteristics of the azoles of interest, to recognize the differences in pharmacology, pharmacokinetics, spectrum of activity, safety, toxicity and potential drug interactions of these antifungal agents.

However, the present review explore that the azoles of interest are sufficiently diverse in pharmacology, pharmacokinetics, spectrum of activity, safety, toxicity and potential drug interactions allowing specialists to differentiate among these agents based upon their characteristics when tailoring therapy to meet the needs of a particular patient. Moreover, further advances in antifungal chemotherapy will be necessary to improve management of invasive mycoses in the future.


Download data is not yet available.


Jone EB. Antimicrobial agents: Antifungal agents, in Goodman and Gilman’sâ€, The Pharmacological Basis of Therapeutics 11th ed. Laurence LB, Chabner BA, Knollmann BC, Eds. McGraw-Hill Inc Health Professions Division: New York; 2011.

Gubbins P, Anaissie E. Overview of Antifungal Agents. Pharmacy Practice News†special edition; 2006.

Don Sheppard MD, Harry WL. Antifungal agents, in Basic and Clinical Pharmacologyâ€, 9th ed. Katzung, Eds, Norwalk, Connecticut: Appleton and Lange; 2004.

Fromtling Ra. Overview of medically important antifungal azole derivatives. Clin Microbiol Rev 1988;1(2):187–217.

Ralph HR, Roy LH. Antifungal agents, in Principles of Pharmacologyâ€, Basic Concepts & Clinical Applications, Paul LM, Robert AM, George RB, Eds. Chapman and Hall, New York: Chapter 98; 1999.

Remington. The Science and Practice of Pharmacyâ€. 20th ed. 2006;13:1674.

Kathleen P. Antifungal agents, In Martindele: The Complete Drug Referenceâ€, The Pharmaceutical Press, 33th ed. London; 2002. p. 391,.

Gubbins PO. The systemically acting azoles, in: Fungal Infections in the Immunocompromised Patientâ€, Wingard J, Anaissie E, eds Boca Raton, Fla: Taylor and Francis Group; 2005. p. 457-84.

Saag SM, Dismukes EW. Azole antifungal agents: Emphasis on new triazolesâ€. Antimicrobial Agents Chemother 1988;32:1-8.

Richard DH, Mary JM. Antifungal agents, in Lippincott’s Illustrated Reviews: Pharmacologyâ€, 3rd ed. Richard AH, Pamela C, Eds. Lippincott Williams and Wilkins, New York; 2006.

Eicher T, Hauptmann S. The Chemistry of Heterocycles: Structure, Reactions, Synthesis, and Applicationsâ€, 2nd ed. John Wiley and Sons; 2003.

Collin D, Clotrimazole, in Therapeutic Drugsâ€, 2nd ed. Churchill Livingstone, New York; 1999. p. 305.

Collin D, Econazole, in Therapeutic Drugsâ€, 2nd ed. Churchill Livingstone, New York; 1999. p. 171.

Collin D, Miconazole nitrate, in Therapeutic Drugsâ€. 2nd ed. Churchill Livingstone, New York; 1999;2:m171.

Collin D, Ketoconazole, in Therapeutic Drugsâ€, 2nd ed. Churchill Livingstone, New York; 1999;2:k13.

Butaconazole, in AHFS, Drug Informationâ€, 2nd ed. American Society of Health system Pharmaceutics, Gerald KM, and Elaine KS, (Eds.) New York; 2010. p. 533.

Collin D. Teraconazole, in Therapeutic Drugsâ€, 2nd ed. Churchill Livingstone, New York; 1999;2:t123.

Collin D. Fluconazole, in Therapeutic Drugsâ€, 2nd ed. Churchill Livingstone, New York; 1999;2:f62.

Collin D. Itraconazole, in Therapeutic Drugsâ€, 2nd ed. Churchill Livingstone, New York; 1999;2:i120.

Voriconazole, in AHFS, Drug Informationâ€, 2nd ed. American Society of Health system Pharmaceutics, Gerald KM, Elaine KS. (Eds.) New York; 2010. p. 541.

Ghannoum MA, Rice LB. Antifungal agents: mode of action, mechanisms of resistance, and correlation of these mechanisms with bacterial resistanceâ€. Clin Microbiol Rev 1999;12:501.

Pfaller MA, Messer SA, Hollis RJ, Jones RN. In vitro activities of posaconazole (SCH 56592) compared with those of itraconazole and fluconazole against 3,685 clinical isolates of Candida species. and Cryptococcus neoformansâ€. Antimicrob Agents Chemother 2001;45:2862.

Pfaller MA, Boyken L, Hollis RJ, Messer SA, Tendolkar S, Diekema DJ. In vitro susceptibilities of clinical isolates of Candida species, Cryptococcus neoformans, and Aspergillus species to itraconazole: global survey of 9,359 isolates tested by clinical and laboratory standards institute broth microdilution methodsâ€. J Clin Microbiol 2005;43:3807.

Fothergill AW. Miconazole: A historical perspectiveâ€. Expert Rev Anti-infect Ther 2006;4(2):171-5.

Pershing KL, Corlett J, Jorgensen C. In-vivo pharmacokinetics and pharmacodynamics of topical Ketoconazole and Miconazole in human stratum corneumâ€. Antimicrobial Agents Chemother 1994;38:90-5.

Gonzalez GM, Fothergill AW, Sutton DA, Rinaldi MG, Loebenberg D. In vitro activities of new and established triazoles against opportunistic filamentous and dimorphic fungiâ€. Med Mycol 2005;43:281.

Sanati H, Belanger P, Rutilio F, Ghannoum M. A new triazole, voriconazole (UK-109,496), blocks sterol biosynthesis in candida albicans and candida kruseiâ€. Antimicrob Agents Chemother 1997;2441:2492.

Ally R, Schürmann D, Kreisel W, Carosi G, Aguirrebengoa K, Dupont B, et al. "A randomized, double-blind, double-dummy, multicenter trial of voriconazole and fluconazole in the treatment of esophageal candidiasis in immunocompromised patients". Clin Infect Dis 2001;33(9):1447–54.

David A. Antifungal agents pharmacokinetics and pharmacodynamics of amphotericin, in "Antimicrobial Pharmacodynamics in Theory and Clinical Practice", 2nd ed. Charles HN, Paul GA, George LD, Takeo M. Eds. CRC Press; 2007. p. 315–26.

Johan WM. Pharmacokinetics and Pharmacodynamics of Azoles, in "Antimicrobial Pharmacodynamics in Theory and Clinical Practice", 2nd ed. Charles HN, Paul GA, George LD, Takeo M. CRC Press; 2007. p. 327–53.

Blum RA, D'Andrea DT, Florentino BM. Increased gastric pH and the bioavailability of fluconazole and ketoconazole. Ann Intern Med 1991;114:755.

Venkatakrishnan K, Von Moltke LL, Greenblatt DJ. Effects of the antifungal agents on oxidative drug metabolism: clinical relevance. Clin Pharmacokinet 2000;38:111–80.

Niwa T, Shiraga T, Takagi A. Effect of antifungal drugs on cytochrome P450 (CYP) 2C9, CYP2C19, and CYP3A4 activities in human liver microsomes. Biol Pharm Bull 2005;28(9):1805-8.

Bellmann R. Clinical pharmacokinetics of systemically administered antimycotics. Curr Clin Pharmacol 2007;2:37.

Boucher HW, Groll AH, Chiou CC, Walsh TJ. Newer systemic antifungal agents: pharmacokinetics, safety and efficacy. Drugs 2004;64:1997.

Zonios DI, Bennett JE. Update on azole antifungals. Semin Respir Crit Care Med 2008;29:198.

Miyama T, Takanaga H, Matsuo H. P-glycoprotein-mediated transport of itraconazole across the blood-brain barrier. Antimicrob Agents Chemother 1998;42(7):1738-44.

Pappas PG, Kauffman CA, Perfect J. Alopecia associated with fluconazole therapy. Ann Intern Med 1995;123:354.

Tan K, Brayshaw N, Tomaszewski K, Troke P, Wood N. Investigation of the potential relationships between plasma voriconazole concentrations and visual adverse events or liver function test abnormalities. J Clin Pharmacol 2006;46(2):235-43.

Ahmad SR, Singer SJ, Leissa BG. Congestive heart failure associated with itraconazole. Lancet 2001;357:1766.

Gubbins PO, McConnell SA, Amsden JR. Drug interactions associated with antifungal agents. In: Piscitelli SC, Rodvold KA, eds. Drug Interactions in Infectious Diseases. Totowa, NJ: Humana Press; 2005. p. 289-337.

Gubbins PO, Amsden JR. Drug-drug interactions of antifungal agents and implications for patient care. Expert Opin Pharmacother 2005;6(13):2231-43.

Piscitelli SC, Goss TF, Wilton JH, D’Andrea DT, Goldstein H, Schentag JJ. Effects of ranitidine and sucralfate on ketoconazole bioavailability. Antimicrob Agents Chemother 1991;35(9):1765-71.

Wang EJ, Lew K, Casciano CN, Clement RP, Johnson WW. Interaction of common azole antifungals with P glycoprotein. Antimicrob Agents Chemother 2002;46(1):160-5.

Mishra NN, Prasad T, Sharma N, Payasi R, Gupta DK, Singh R. Pathogenicity and drug resistance in Candida albicans and other yeast species. Acta Microbiol Immunol Hung 2007;54(3):201-35.

He X, Tiballi RN, Zarins LT, Bradley SF, Sangeorzan JA, Kauffman CA. Azole resistance in oropharyngeal Candida albicans strains isolated from patients infected with human immunodeficiency virus. Antimicrob Agents Chemother 1994;38:2495.

Thomas-Greber E, Korting HC, Bogner J, Goebel FD. Fluconazole-resistant oral candidosis in a repeatedly treated female AIDS patient. Mycoses 1994;37:35.

White TC, Marr KA, Bowden RA. Clinical, cellular, and molecular factors that contribute to antifungal drug resistance. Clin Microbiol Rev 1998;11:382.

Lupetti A, Danesi R, Campa M, Del Tacca M, Kelly S. Molecular basis of resistance to azole antifungals. Trends Mol Med 2002;8:76.

Zeina AK, John RP. Resistance to antifungal agents: mechanisms and clinical impact. Clin Infect Dis 2008;46(1):120-8.



How to Cite

El-garhy, O. H. “AN OVERVIEW OF THE AZOLES OF INTEREST”. International Journal of Current Pharmaceutical Research, vol. 7, no. 1, Jan. 2015, pp. 1-6,



Review Article(s)