Pharmacokinetics of antifungal drugs: practical implications for optimized treatment of patients
| Autor: | Piotr Smuszkiewicz, Romuald Bellmann |
|---|---|
| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
Microbiology (medical) Antifungal Agents Itraconazole 030106 microbiology Liposomal amphotericin B Review Polyenes Pharmacology Flucytosine Echinocandins 03 medical and health sciences chemistry.chemical_compound Caspofungin Amphotericin B medicine Humans Drug Interactions Tissue Distribution Critically ill Voriconazole Extracorporeal membrane oxygenation Renal replacement therapy business.industry Amphotericin B lipid formulations Micafungin General Medicine bacterial infections and mycoses medicine.disease Infectious Diseases Mycoses chemistry Cryptococcosis Anidulafungin Drug Therapy Combination business medicine.drug |
| Zdroj: | Infection |
| ISSN: | 1439-0973 0300-8126 |
| DOI: | 10.1007/s15010-017-1042-z |
| Popis: | Introduction Because of the high mortality of invasive fungal infections (IFIs), appropriate exposure to antifungals appears to be crucial for therapeutic efficacy and safety. Materials and methods This review summarises published pharmacokinetic data on systemically administered antifungals focusing on co-morbidities, target-site penetration, and combination antifungal therapy. Conclusions and discussion Amphotericin B is eliminated unchanged via urine and faeces. Flucytosine and fluconazole display low protein binding and are eliminated by the kidney. Itraconazole, voriconazole, posaconazole and isavuconazole are metabolised in the liver. Azoles are substrates and inhibitors of cytochrome P450 (CYP) isoenzymes and are therefore involved in numerous drug–drug interactions. Anidulafungin is spontaneously degraded in the plasma. Caspofungin and micafungin undergo enzymatic metabolism in the liver, which is independent of CYP. Although several drug–drug interactions occur during caspofungin and micafungin treatment, echinocandins display a lower potential for drug–drug interactions. Flucytosine and azoles penetrate into most of relevant tissues. Amphotericin B accumulates in the liver and in the spleen. Its concentrations in lung and kidney are intermediate and relatively low myocardium and brain. Tissue distribution of echinocandins is similar to that of amphotericin. Combination antifungal therapy is established for cryptococcosis but controversial in other IFIs such as invasive aspergillosis and mucormycosis. |
| Databáze: | OpenAIRE |
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