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      Pharmacokinetics of voriconazole after a single intramuscular injection in large falcons (Falco spp.)

      Author(s): 1 , 2 , 2 , 1 , 3
      Publication date Created:
      Publication date (Electronic):
      Journal: Medical Mycology
      Publisher: Oxford University Press (OUP)

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          Abstract

          Voriconazole is one of the main azoles used to treat invasive aspergillosis in falconry raptors and birds. Despite the fact that there are studies for oral and intravenous use of voriconazole in birds, there are none for its effect after intramuscular use. Empirical use of intramuscular voriconazole in falcons, indicated quicker therapy response than the oral one. Aim of this study is to evaluate the in vivo pharmacokinetic disposition of injectable voriconazole after a single intramuscular injection in large falcons (i.e., Gyrfalcons, Saker falcons, Peregrine falcons). No clinical side effects were observed in the falcons. Absorption of voriconazole was rapid (0.5–2 hours) and reached a plasma level (>1 μg/ml) which is above the minimal inhibitory concentration (MIC) for all known Aspergillus strains. This level was maintained for 16 to 20 hours, thus indicating that a single injection of 12.5 mg/kg is not enough if T > MIC is taken into consideration. On a newer aspect, according to the AUC24 unbound: MIC parameter would be indicated that this dose would be rather sufficient for most Aspergillus strains.

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          Antifungal agents: mode of action, mechanisms of resistance, and correlation of these mechanisms with bacterial resistance.

          Mahmoud A. Ghannoum, Louis Rice (1999)
          The increased use of antibacterial and antifungal agents in recent years has resulted in the development of resistance to these drugs. The significant clinical implication of resistance has led to heightened interest in the study of antimicrobial resistance from different angles. Areas addressed include mechanisms underlying this resistance, improved methods to detect resistance when it occurs, alternate options for the treatment of infections caused by resistant organisms, and strategies to prevent and control the emergence and spread of resistance. In this review, the mode of action of antifungals and their mechanisms of resistance are discussed. Additionally, an attempt is made to discuss the correlation between fungal and bacterial resistance. Antifungals can be grouped into three classes based on their site of action: azoles, which inhibit the synthesis of ergosterol (the main fungal sterol); polyenes, which interact with fungal membrane sterols physicochemically; and 5-fluorocytosine, which inhibits macromolecular synthesis. Many different types of mechanisms contribute to the development of resistance to antifungals. These mechanisms include alteration in drug target, alteration in sterol biosynthesis, reduction in the intercellular concentration of target enzyme, and overexpression of the antifungal drug target. Although the comparison between the mechanisms of resistance to antifungals and antibacterials is necessarily limited by several factors defined in the review, a correlation between the two exists. For example, modification of enzymes which serve as targets for antimicrobial action and the involvement of membrane pumps in the extrusion of drugs are well characterized in both the eukaryotic and prokaryotic cells.
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            Pharmacokinetic/pharmacodynamic profile of voriconazole.

            Franziska Ihle, Ursula Theuretzbacher, Hartmut Derendorf (2005)
            Voriconazole is the first available second-generation triazole with potent activity against a broad spectrum of clinically significant fungal pathogens, including Aspergillus,Candida, Cryptococcus neoformans, and some less common moulds. Voriconazole is rapidly absorbed within 2 hours after oral administration and the oral bioavailability is over 90%, thus allowing switching between oral and intravenous formulations when clinically appropriate. Voriconazole shows nonlinear pharmacokinetics due to its capacity-limited elimination, and its pharmacokinetics are therefore dependent upon the administered dose. With increasing dose, voriconazole shows a superproportional increase in area under the plasma concentration-time curve (AUC). In doses used in children (age < 12 years) voriconazole pharmacokinetics appear to be linear. Steady-state plasma concentrations are reached approximately 5 days after both intravenous and oral administration; however, steady state is reached within 24 hours with voriconazole administered as an intravenous loading dose. The volume of distribution of voriconazole is 2-4.6 L/kg, suggesting extensive distribution into extracellular and intracellular compartments. Voriconazole was measured in tissue samples of brain, liver, kidney, heart, lung as well as cerebrospinal fluid. The plasma protein binding is about 60% and independent of dose or plasma concentrations. Clearance is hepatic via N-oxidation by the hepatic cytochrome P450 (CYP) isoenzymes, CYP2C19, CYP2C9 and CYP3A4. The elimination half-life of voriconazole is approximately 6 hours, and approximately 80% of the total dose is recovered in the urine, almost completely as metabolites. As with other azole drugs, the potential for drug interactions is considerable. Voriconazole shows time-dependent fungistatic activity against Candida species and time-dependent slow fungicidal activity against Aspergillus species. A short post-antifungal effect of voriconazole is evident only for Aspergillus species. The predictive pharmacokinetic/pharmacodynamic parameter for voriconazole treatment efficacy in Candida infections is the free drug AUC from 0 to 24 hour : minimum inhibitory concentration ratio.
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              Aspergillus and aspergilloses in wild and domestic animals: a global health concern with parallels to human disease.

              Seyedmojtaba Seyedmousavi, Jacques Guillot, Pascal Arné … (2015)
              The importance of aspergillosis in humans and various animal species has increased over the last decades. Aspergillus species are found worldwide in humans and in almost all domestic animals and birds as well as in many wild species, causing a wide range of diseases from localized infections to fatal disseminated diseases, as well as allergic responses to inhaled conidia. Some prevalent forms of animal aspergillosis are invasive fatal infections in sea fan corals, stonebrood mummification in honey bees, pulmonary and air sac infection in birds, mycotic abortion and mammary gland infections in cattle, guttural pouch mycoses in horses, sinonasal infections in dogs and cats, and invasive pulmonary and cerebral infections in marine mammals and nonhuman primates. This article represents a comprehensive overview of the most common infections reported by Aspergillus species and the corresponding diseases in various types of animals.
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                Author and article information

                Journal
                Title: Medical Mycology
                Publisher: Oxford University Press (OUP)
                ISSN (Print): 1369-3786
                ISSN (Electronic): 1460-2709
                Publication date Created: July 2020
                Publication date Created: July 01 2020
                Publication date Created: October 14 2019
                Publication date Other: July 2020
                Publication date (Print): July 01 2020
                Publication date (Electronic): October 14 2019
                Volume: 58
                Issue: 5
                Pages: 661-666
                Affiliations
                [1 ]Dubai Falcon Hospital, Dubai, United Arab Emirates (Azmanis, Silvanose)
                [2 ]Department of Biology, Chemistry and Environmental Studies, American University of Sharjah (AUS), United Arab Emirates (Pappalardo, Sara)
                [3 ]Biomedical Research Center (BRC), Faculty of Veterinary Science, University of Pretoriaz, Republic of South Africa (Naidoo)
                Article
                DOI: 10.1093/mmy/myz102
                SO-VID: cec2458c-f7a5-4624-b58c-c70e9ec59fee
                Copyright © © 2019
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                https://academic.oup.com/journals/pages/open_access/funder_policies/chorus/standard_publication_model

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