Voriconazole pharmacokinetics and exposure–response relationships: Assessing the links between exposure, efficacy and toxicity
The triazole antifungal voriconazole (VCZ) exhibits broad-spectrum antifungal activity and is the first-line treatment for invasive aspergillosis. Highly variable, non-linear pharmacokinetics, metabolism via the polymorphic drug-metabolising enzyme CYP2C19, and a range of serious adverse events (AEs...
Ausführliche Beschreibung
Gespeichert in:
| Autor*in: |
Dolton, Michael J. [verfasserIn] |
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| Format: |
E-Artikel |
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| Sprache: |
Englisch |
| Erschienen: |
2014transfer abstract |
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| Schlagwörter: |
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| Umfang: |
11 |
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| Übergeordnetes Werk: |
Enthalten in: Advanced constraint propagation for the combined car sequencing and level scheduling problem - Yavuz, Mesut ELSEVIER, 2018, Amsterdam [u.a.] |
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| Übergeordnetes Werk: |
volume:44 ; year:2014 ; number:3 ; pages:183-193 ; extent:11 |
| Links: |
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| DOI / URN: |
10.1016/j.ijantimicag.2014.05.019 |
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| 520 | |a The triazole antifungal voriconazole (VCZ) exhibits broad-spectrum antifungal activity and is the first-line treatment for invasive aspergillosis. Highly variable, non-linear pharmacokinetics, metabolism via the polymorphic drug-metabolising enzyme CYP2C19, and a range of serious adverse events (AEs) including hepatotoxicity and neurotoxicity complicate the clinical utility of VCZ. As interest in optimising VCZ treatment has increased, a growing number of studies have examined the relationships between VCZ exposure and efficacy in the treatment and prevention of invasive fungal infections, as well as associations with VCZ-related AEs. This review provides a critical analysis of VCZ pharmacokinetics and exposure–response (E-R) relationships, assessing the links between VCZ exposure, efficacy and toxicity. Low VCZ exposure has frequently been associated with a higher incidence of treatment failure; fewer studies have addressed E-R relationships with prophylactic VCZ. VCZ-related neurotoxicity appears common at high VCZ concentrations and can be minimised by maintaining concentrations below the recommended upper concentration thresholds; hepatotoxicity appears to be associated with increased VCZ exposure but is also prevalent at low concentrations. Further research should aim to inform and optimise the narrow therapeutic range of VCZ as well as develop interventions to individualise VCZ dosing to achieve maximal efficacy with minimal toxicity. | ||
| 520 | |a The triazole antifungal voriconazole (VCZ) exhibits broad-spectrum antifungal activity and is the first-line treatment for invasive aspergillosis. Highly variable, non-linear pharmacokinetics, metabolism via the polymorphic drug-metabolising enzyme CYP2C19, and a range of serious adverse events (AEs) including hepatotoxicity and neurotoxicity complicate the clinical utility of VCZ. As interest in optimising VCZ treatment has increased, a growing number of studies have examined the relationships between VCZ exposure and efficacy in the treatment and prevention of invasive fungal infections, as well as associations with VCZ-related AEs. This review provides a critical analysis of VCZ pharmacokinetics and exposure–response (E-R) relationships, assessing the links between VCZ exposure, efficacy and toxicity. Low VCZ exposure has frequently been associated with a higher incidence of treatment failure; fewer studies have addressed E-R relationships with prophylactic VCZ. VCZ-related neurotoxicity appears common at high VCZ concentrations and can be minimised by maintaining concentrations below the recommended upper concentration thresholds; hepatotoxicity appears to be associated with increased VCZ exposure but is also prevalent at low concentrations. Further research should aim to inform and optimise the narrow therapeutic range of VCZ as well as develop interventions to individualise VCZ dosing to achieve maximal efficacy with minimal toxicity. | ||
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| 650 | 7 | |a Exposure–response |2 Elsevier | |
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10.1016/j.ijantimicag.2014.05.019 doi GBVA2014014000021.pica (DE-627)ELV012416398 (ELSEVIER)S0924-8579(14)00185-X DE-627 ger DE-627 rakwb eng 610 610 DE-600 650 VZ 85.03 bkl 31.80 bkl 54.80 bkl 50.03 bkl Dolton, Michael J. verfasserin aut Voriconazole pharmacokinetics and exposure–response relationships: Assessing the links between exposure, efficacy and toxicity 2014transfer abstract 11 nicht spezifiziert zzz rdacontent nicht spezifiziert z rdamedia nicht spezifiziert zu rdacarrier The triazole antifungal voriconazole (VCZ) exhibits broad-spectrum antifungal activity and is the first-line treatment for invasive aspergillosis. Highly variable, non-linear pharmacokinetics, metabolism via the polymorphic drug-metabolising enzyme CYP2C19, and a range of serious adverse events (AEs) including hepatotoxicity and neurotoxicity complicate the clinical utility of VCZ. As interest in optimising VCZ treatment has increased, a growing number of studies have examined the relationships between VCZ exposure and efficacy in the treatment and prevention of invasive fungal infections, as well as associations with VCZ-related AEs. This review provides a critical analysis of VCZ pharmacokinetics and exposure–response (E-R) relationships, assessing the links between VCZ exposure, efficacy and toxicity. Low VCZ exposure has frequently been associated with a higher incidence of treatment failure; fewer studies have addressed E-R relationships with prophylactic VCZ. VCZ-related neurotoxicity appears common at high VCZ concentrations and can be minimised by maintaining concentrations below the recommended upper concentration thresholds; hepatotoxicity appears to be associated with increased VCZ exposure but is also prevalent at low concentrations. Further research should aim to inform and optimise the narrow therapeutic range of VCZ as well as develop interventions to individualise VCZ dosing to achieve maximal efficacy with minimal toxicity. The triazole antifungal voriconazole (VCZ) exhibits broad-spectrum antifungal activity and is the first-line treatment for invasive aspergillosis. Highly variable, non-linear pharmacokinetics, metabolism via the polymorphic drug-metabolising enzyme CYP2C19, and a range of serious adverse events (AEs) including hepatotoxicity and neurotoxicity complicate the clinical utility of VCZ. As interest in optimising VCZ treatment has increased, a growing number of studies have examined the relationships between VCZ exposure and efficacy in the treatment and prevention of invasive fungal infections, as well as associations with VCZ-related AEs. This review provides a critical analysis of VCZ pharmacokinetics and exposure–response (E-R) relationships, assessing the links between VCZ exposure, efficacy and toxicity. Low VCZ exposure has frequently been associated with a higher incidence of treatment failure; fewer studies have addressed E-R relationships with prophylactic VCZ. VCZ-related neurotoxicity appears common at high VCZ concentrations and can be minimised by maintaining concentrations below the recommended upper concentration thresholds; hepatotoxicity appears to be associated with increased VCZ exposure but is also prevalent at low concentrations. Further research should aim to inform and optimise the narrow therapeutic range of VCZ as well as develop interventions to individualise VCZ dosing to achieve maximal efficacy with minimal toxicity. Azoles Elsevier Pharmacodynamics Elsevier Antifungal Elsevier Voriconazole Elsevier Exposure–response Elsevier Pharmacokinetics Elsevier McLachlan, Andrew J. oth Enthalten in Elsevier Science Yavuz, Mesut ELSEVIER Advanced constraint propagation for the combined car sequencing and level scheduling problem 2018 Amsterdam [u.a.] (DE-627)ELV000585106 volume:44 year:2014 number:3 pages:183-193 extent:11 https://doi.org/10.1016/j.ijantimicag.2014.05.019 Volltext GBV_USEFLAG_U GBV_ELV SYSFLAG_U SSG-OPC-MAT 85.03 Methoden und Techniken der Betriebswirtschaft VZ 31.80 Angewandte Mathematik VZ 54.80 Angewandte Informatik VZ 50.03 Methoden und Techniken der Ingenieurwissenschaften VZ AR 44 2014 3 183-193 11 045F 610 |
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10.1016/j.ijantimicag.2014.05.019 doi GBVA2014014000021.pica (DE-627)ELV012416398 (ELSEVIER)S0924-8579(14)00185-X DE-627 ger DE-627 rakwb eng 610 610 DE-600 650 VZ 85.03 bkl 31.80 bkl 54.80 bkl 50.03 bkl Dolton, Michael J. verfasserin aut Voriconazole pharmacokinetics and exposure–response relationships: Assessing the links between exposure, efficacy and toxicity 2014transfer abstract 11 nicht spezifiziert zzz rdacontent nicht spezifiziert z rdamedia nicht spezifiziert zu rdacarrier The triazole antifungal voriconazole (VCZ) exhibits broad-spectrum antifungal activity and is the first-line treatment for invasive aspergillosis. Highly variable, non-linear pharmacokinetics, metabolism via the polymorphic drug-metabolising enzyme CYP2C19, and a range of serious adverse events (AEs) including hepatotoxicity and neurotoxicity complicate the clinical utility of VCZ. As interest in optimising VCZ treatment has increased, a growing number of studies have examined the relationships between VCZ exposure and efficacy in the treatment and prevention of invasive fungal infections, as well as associations with VCZ-related AEs. This review provides a critical analysis of VCZ pharmacokinetics and exposure–response (E-R) relationships, assessing the links between VCZ exposure, efficacy and toxicity. Low VCZ exposure has frequently been associated with a higher incidence of treatment failure; fewer studies have addressed E-R relationships with prophylactic VCZ. VCZ-related neurotoxicity appears common at high VCZ concentrations and can be minimised by maintaining concentrations below the recommended upper concentration thresholds; hepatotoxicity appears to be associated with increased VCZ exposure but is also prevalent at low concentrations. Further research should aim to inform and optimise the narrow therapeutic range of VCZ as well as develop interventions to individualise VCZ dosing to achieve maximal efficacy with minimal toxicity. The triazole antifungal voriconazole (VCZ) exhibits broad-spectrum antifungal activity and is the first-line treatment for invasive aspergillosis. Highly variable, non-linear pharmacokinetics, metabolism via the polymorphic drug-metabolising enzyme CYP2C19, and a range of serious adverse events (AEs) including hepatotoxicity and neurotoxicity complicate the clinical utility of VCZ. As interest in optimising VCZ treatment has increased, a growing number of studies have examined the relationships between VCZ exposure and efficacy in the treatment and prevention of invasive fungal infections, as well as associations with VCZ-related AEs. This review provides a critical analysis of VCZ pharmacokinetics and exposure–response (E-R) relationships, assessing the links between VCZ exposure, efficacy and toxicity. Low VCZ exposure has frequently been associated with a higher incidence of treatment failure; fewer studies have addressed E-R relationships with prophylactic VCZ. VCZ-related neurotoxicity appears common at high VCZ concentrations and can be minimised by maintaining concentrations below the recommended upper concentration thresholds; hepatotoxicity appears to be associated with increased VCZ exposure but is also prevalent at low concentrations. Further research should aim to inform and optimise the narrow therapeutic range of VCZ as well as develop interventions to individualise VCZ dosing to achieve maximal efficacy with minimal toxicity. Azoles Elsevier Pharmacodynamics Elsevier Antifungal Elsevier Voriconazole Elsevier Exposure–response Elsevier Pharmacokinetics Elsevier McLachlan, Andrew J. oth Enthalten in Elsevier Science Yavuz, Mesut ELSEVIER Advanced constraint propagation for the combined car sequencing and level scheduling problem 2018 Amsterdam [u.a.] (DE-627)ELV000585106 volume:44 year:2014 number:3 pages:183-193 extent:11 https://doi.org/10.1016/j.ijantimicag.2014.05.019 Volltext GBV_USEFLAG_U GBV_ELV SYSFLAG_U SSG-OPC-MAT 85.03 Methoden und Techniken der Betriebswirtschaft VZ 31.80 Angewandte Mathematik VZ 54.80 Angewandte Informatik VZ 50.03 Methoden und Techniken der Ingenieurwissenschaften VZ AR 44 2014 3 183-193 11 045F 610 |
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10.1016/j.ijantimicag.2014.05.019 doi GBVA2014014000021.pica (DE-627)ELV012416398 (ELSEVIER)S0924-8579(14)00185-X DE-627 ger DE-627 rakwb eng 610 610 DE-600 650 VZ 85.03 bkl 31.80 bkl 54.80 bkl 50.03 bkl Dolton, Michael J. verfasserin aut Voriconazole pharmacokinetics and exposure–response relationships: Assessing the links between exposure, efficacy and toxicity 2014transfer abstract 11 nicht spezifiziert zzz rdacontent nicht spezifiziert z rdamedia nicht spezifiziert zu rdacarrier The triazole antifungal voriconazole (VCZ) exhibits broad-spectrum antifungal activity and is the first-line treatment for invasive aspergillosis. Highly variable, non-linear pharmacokinetics, metabolism via the polymorphic drug-metabolising enzyme CYP2C19, and a range of serious adverse events (AEs) including hepatotoxicity and neurotoxicity complicate the clinical utility of VCZ. As interest in optimising VCZ treatment has increased, a growing number of studies have examined the relationships between VCZ exposure and efficacy in the treatment and prevention of invasive fungal infections, as well as associations with VCZ-related AEs. This review provides a critical analysis of VCZ pharmacokinetics and exposure–response (E-R) relationships, assessing the links between VCZ exposure, efficacy and toxicity. Low VCZ exposure has frequently been associated with a higher incidence of treatment failure; fewer studies have addressed E-R relationships with prophylactic VCZ. VCZ-related neurotoxicity appears common at high VCZ concentrations and can be minimised by maintaining concentrations below the recommended upper concentration thresholds; hepatotoxicity appears to be associated with increased VCZ exposure but is also prevalent at low concentrations. Further research should aim to inform and optimise the narrow therapeutic range of VCZ as well as develop interventions to individualise VCZ dosing to achieve maximal efficacy with minimal toxicity. The triazole antifungal voriconazole (VCZ) exhibits broad-spectrum antifungal activity and is the first-line treatment for invasive aspergillosis. Highly variable, non-linear pharmacokinetics, metabolism via the polymorphic drug-metabolising enzyme CYP2C19, and a range of serious adverse events (AEs) including hepatotoxicity and neurotoxicity complicate the clinical utility of VCZ. As interest in optimising VCZ treatment has increased, a growing number of studies have examined the relationships between VCZ exposure and efficacy in the treatment and prevention of invasive fungal infections, as well as associations with VCZ-related AEs. This review provides a critical analysis of VCZ pharmacokinetics and exposure–response (E-R) relationships, assessing the links between VCZ exposure, efficacy and toxicity. Low VCZ exposure has frequently been associated with a higher incidence of treatment failure; fewer studies have addressed E-R relationships with prophylactic VCZ. VCZ-related neurotoxicity appears common at high VCZ concentrations and can be minimised by maintaining concentrations below the recommended upper concentration thresholds; hepatotoxicity appears to be associated with increased VCZ exposure but is also prevalent at low concentrations. Further research should aim to inform and optimise the narrow therapeutic range of VCZ as well as develop interventions to individualise VCZ dosing to achieve maximal efficacy with minimal toxicity. Azoles Elsevier Pharmacodynamics Elsevier Antifungal Elsevier Voriconazole Elsevier Exposure–response Elsevier Pharmacokinetics Elsevier McLachlan, Andrew J. oth Enthalten in Elsevier Science Yavuz, Mesut ELSEVIER Advanced constraint propagation for the combined car sequencing and level scheduling problem 2018 Amsterdam [u.a.] (DE-627)ELV000585106 volume:44 year:2014 number:3 pages:183-193 extent:11 https://doi.org/10.1016/j.ijantimicag.2014.05.019 Volltext GBV_USEFLAG_U GBV_ELV SYSFLAG_U SSG-OPC-MAT 85.03 Methoden und Techniken der Betriebswirtschaft VZ 31.80 Angewandte Mathematik VZ 54.80 Angewandte Informatik VZ 50.03 Methoden und Techniken der Ingenieurwissenschaften VZ AR 44 2014 3 183-193 11 045F 610 |
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10.1016/j.ijantimicag.2014.05.019 doi GBVA2014014000021.pica (DE-627)ELV012416398 (ELSEVIER)S0924-8579(14)00185-X DE-627 ger DE-627 rakwb eng 610 610 DE-600 650 VZ 85.03 bkl 31.80 bkl 54.80 bkl 50.03 bkl Dolton, Michael J. verfasserin aut Voriconazole pharmacokinetics and exposure–response relationships: Assessing the links between exposure, efficacy and toxicity 2014transfer abstract 11 nicht spezifiziert zzz rdacontent nicht spezifiziert z rdamedia nicht spezifiziert zu rdacarrier The triazole antifungal voriconazole (VCZ) exhibits broad-spectrum antifungal activity and is the first-line treatment for invasive aspergillosis. Highly variable, non-linear pharmacokinetics, metabolism via the polymorphic drug-metabolising enzyme CYP2C19, and a range of serious adverse events (AEs) including hepatotoxicity and neurotoxicity complicate the clinical utility of VCZ. As interest in optimising VCZ treatment has increased, a growing number of studies have examined the relationships between VCZ exposure and efficacy in the treatment and prevention of invasive fungal infections, as well as associations with VCZ-related AEs. This review provides a critical analysis of VCZ pharmacokinetics and exposure–response (E-R) relationships, assessing the links between VCZ exposure, efficacy and toxicity. Low VCZ exposure has frequently been associated with a higher incidence of treatment failure; fewer studies have addressed E-R relationships with prophylactic VCZ. VCZ-related neurotoxicity appears common at high VCZ concentrations and can be minimised by maintaining concentrations below the recommended upper concentration thresholds; hepatotoxicity appears to be associated with increased VCZ exposure but is also prevalent at low concentrations. Further research should aim to inform and optimise the narrow therapeutic range of VCZ as well as develop interventions to individualise VCZ dosing to achieve maximal efficacy with minimal toxicity. The triazole antifungal voriconazole (VCZ) exhibits broad-spectrum antifungal activity and is the first-line treatment for invasive aspergillosis. Highly variable, non-linear pharmacokinetics, metabolism via the polymorphic drug-metabolising enzyme CYP2C19, and a range of serious adverse events (AEs) including hepatotoxicity and neurotoxicity complicate the clinical utility of VCZ. As interest in optimising VCZ treatment has increased, a growing number of studies have examined the relationships between VCZ exposure and efficacy in the treatment and prevention of invasive fungal infections, as well as associations with VCZ-related AEs. This review provides a critical analysis of VCZ pharmacokinetics and exposure–response (E-R) relationships, assessing the links between VCZ exposure, efficacy and toxicity. Low VCZ exposure has frequently been associated with a higher incidence of treatment failure; fewer studies have addressed E-R relationships with prophylactic VCZ. VCZ-related neurotoxicity appears common at high VCZ concentrations and can be minimised by maintaining concentrations below the recommended upper concentration thresholds; hepatotoxicity appears to be associated with increased VCZ exposure but is also prevalent at low concentrations. Further research should aim to inform and optimise the narrow therapeutic range of VCZ as well as develop interventions to individualise VCZ dosing to achieve maximal efficacy with minimal toxicity. Azoles Elsevier Pharmacodynamics Elsevier Antifungal Elsevier Voriconazole Elsevier Exposure–response Elsevier Pharmacokinetics Elsevier McLachlan, Andrew J. oth Enthalten in Elsevier Science Yavuz, Mesut ELSEVIER Advanced constraint propagation for the combined car sequencing and level scheduling problem 2018 Amsterdam [u.a.] (DE-627)ELV000585106 volume:44 year:2014 number:3 pages:183-193 extent:11 https://doi.org/10.1016/j.ijantimicag.2014.05.019 Volltext GBV_USEFLAG_U GBV_ELV SYSFLAG_U SSG-OPC-MAT 85.03 Methoden und Techniken der Betriebswirtschaft VZ 31.80 Angewandte Mathematik VZ 54.80 Angewandte Informatik VZ 50.03 Methoden und Techniken der Ingenieurwissenschaften VZ AR 44 2014 3 183-193 11 045F 610 |
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10.1016/j.ijantimicag.2014.05.019 doi GBVA2014014000021.pica (DE-627)ELV012416398 (ELSEVIER)S0924-8579(14)00185-X DE-627 ger DE-627 rakwb eng 610 610 DE-600 650 VZ 85.03 bkl 31.80 bkl 54.80 bkl 50.03 bkl Dolton, Michael J. verfasserin aut Voriconazole pharmacokinetics and exposure–response relationships: Assessing the links between exposure, efficacy and toxicity 2014transfer abstract 11 nicht spezifiziert zzz rdacontent nicht spezifiziert z rdamedia nicht spezifiziert zu rdacarrier The triazole antifungal voriconazole (VCZ) exhibits broad-spectrum antifungal activity and is the first-line treatment for invasive aspergillosis. Highly variable, non-linear pharmacokinetics, metabolism via the polymorphic drug-metabolising enzyme CYP2C19, and a range of serious adverse events (AEs) including hepatotoxicity and neurotoxicity complicate the clinical utility of VCZ. As interest in optimising VCZ treatment has increased, a growing number of studies have examined the relationships between VCZ exposure and efficacy in the treatment and prevention of invasive fungal infections, as well as associations with VCZ-related AEs. This review provides a critical analysis of VCZ pharmacokinetics and exposure–response (E-R) relationships, assessing the links between VCZ exposure, efficacy and toxicity. Low VCZ exposure has frequently been associated with a higher incidence of treatment failure; fewer studies have addressed E-R relationships with prophylactic VCZ. VCZ-related neurotoxicity appears common at high VCZ concentrations and can be minimised by maintaining concentrations below the recommended upper concentration thresholds; hepatotoxicity appears to be associated with increased VCZ exposure but is also prevalent at low concentrations. Further research should aim to inform and optimise the narrow therapeutic range of VCZ as well as develop interventions to individualise VCZ dosing to achieve maximal efficacy with minimal toxicity. The triazole antifungal voriconazole (VCZ) exhibits broad-spectrum antifungal activity and is the first-line treatment for invasive aspergillosis. Highly variable, non-linear pharmacokinetics, metabolism via the polymorphic drug-metabolising enzyme CYP2C19, and a range of serious adverse events (AEs) including hepatotoxicity and neurotoxicity complicate the clinical utility of VCZ. As interest in optimising VCZ treatment has increased, a growing number of studies have examined the relationships between VCZ exposure and efficacy in the treatment and prevention of invasive fungal infections, as well as associations with VCZ-related AEs. This review provides a critical analysis of VCZ pharmacokinetics and exposure–response (E-R) relationships, assessing the links between VCZ exposure, efficacy and toxicity. Low VCZ exposure has frequently been associated with a higher incidence of treatment failure; fewer studies have addressed E-R relationships with prophylactic VCZ. VCZ-related neurotoxicity appears common at high VCZ concentrations and can be minimised by maintaining concentrations below the recommended upper concentration thresholds; hepatotoxicity appears to be associated with increased VCZ exposure but is also prevalent at low concentrations. Further research should aim to inform and optimise the narrow therapeutic range of VCZ as well as develop interventions to individualise VCZ dosing to achieve maximal efficacy with minimal toxicity. Azoles Elsevier Pharmacodynamics Elsevier Antifungal Elsevier Voriconazole Elsevier Exposure–response Elsevier Pharmacokinetics Elsevier McLachlan, Andrew J. oth Enthalten in Elsevier Science Yavuz, Mesut ELSEVIER Advanced constraint propagation for the combined car sequencing and level scheduling problem 2018 Amsterdam [u.a.] (DE-627)ELV000585106 volume:44 year:2014 number:3 pages:183-193 extent:11 https://doi.org/10.1016/j.ijantimicag.2014.05.019 Volltext GBV_USEFLAG_U GBV_ELV SYSFLAG_U SSG-OPC-MAT 85.03 Methoden und Techniken der Betriebswirtschaft VZ 31.80 Angewandte Mathematik VZ 54.80 Angewandte Informatik VZ 50.03 Methoden und Techniken der Ingenieurwissenschaften VZ AR 44 2014 3 183-193 11 045F 610 |
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The triazole antifungal voriconazole (VCZ) exhibits broad-spectrum antifungal activity and is the first-line treatment for invasive aspergillosis. Highly variable, non-linear pharmacokinetics, metabolism via the polymorphic drug-metabolising enzyme CYP2C19, and a range of serious adverse events (AEs) including hepatotoxicity and neurotoxicity complicate the clinical utility of VCZ. As interest in optimising VCZ treatment has increased, a growing number of studies have examined the relationships between VCZ exposure and efficacy in the treatment and prevention of invasive fungal infections, as well as associations with VCZ-related AEs. This review provides a critical analysis of VCZ pharmacokinetics and exposure–response (E-R) relationships, assessing the links between VCZ exposure, efficacy and toxicity. Low VCZ exposure has frequently been associated with a higher incidence of treatment failure; fewer studies have addressed E-R relationships with prophylactic VCZ. VCZ-related neurotoxicity appears common at high VCZ concentrations and can be minimised by maintaining concentrations below the recommended upper concentration thresholds; hepatotoxicity appears to be associated with increased VCZ exposure but is also prevalent at low concentrations. Further research should aim to inform and optimise the narrow therapeutic range of VCZ as well as develop interventions to individualise VCZ dosing to achieve maximal efficacy with minimal toxicity. |
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The triazole antifungal voriconazole (VCZ) exhibits broad-spectrum antifungal activity and is the first-line treatment for invasive aspergillosis. Highly variable, non-linear pharmacokinetics, metabolism via the polymorphic drug-metabolising enzyme CYP2C19, and a range of serious adverse events (AEs) including hepatotoxicity and neurotoxicity complicate the clinical utility of VCZ. As interest in optimising VCZ treatment has increased, a growing number of studies have examined the relationships between VCZ exposure and efficacy in the treatment and prevention of invasive fungal infections, as well as associations with VCZ-related AEs. This review provides a critical analysis of VCZ pharmacokinetics and exposure–response (E-R) relationships, assessing the links between VCZ exposure, efficacy and toxicity. Low VCZ exposure has frequently been associated with a higher incidence of treatment failure; fewer studies have addressed E-R relationships with prophylactic VCZ. VCZ-related neurotoxicity appears common at high VCZ concentrations and can be minimised by maintaining concentrations below the recommended upper concentration thresholds; hepatotoxicity appears to be associated with increased VCZ exposure but is also prevalent at low concentrations. Further research should aim to inform and optimise the narrow therapeutic range of VCZ as well as develop interventions to individualise VCZ dosing to achieve maximal efficacy with minimal toxicity. |
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The triazole antifungal voriconazole (VCZ) exhibits broad-spectrum antifungal activity and is the first-line treatment for invasive aspergillosis. Highly variable, non-linear pharmacokinetics, metabolism via the polymorphic drug-metabolising enzyme CYP2C19, and a range of serious adverse events (AEs) including hepatotoxicity and neurotoxicity complicate the clinical utility of VCZ. As interest in optimising VCZ treatment has increased, a growing number of studies have examined the relationships between VCZ exposure and efficacy in the treatment and prevention of invasive fungal infections, as well as associations with VCZ-related AEs. This review provides a critical analysis of VCZ pharmacokinetics and exposure–response (E-R) relationships, assessing the links between VCZ exposure, efficacy and toxicity. Low VCZ exposure has frequently been associated with a higher incidence of treatment failure; fewer studies have addressed E-R relationships with prophylactic VCZ. VCZ-related neurotoxicity appears common at high VCZ concentrations and can be minimised by maintaining concentrations below the recommended upper concentration thresholds; hepatotoxicity appears to be associated with increased VCZ exposure but is also prevalent at low concentrations. Further research should aim to inform and optimise the narrow therapeutic range of VCZ as well as develop interventions to individualise VCZ dosing to achieve maximal efficacy with minimal toxicity. |
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