Pharmacokinetics, Safety, and Efficacy of Posaconazole in Patients with Persistent Febrile Neutropenia or Refractory Invasive Fungal Infection

Ullmann, Andrew J.; Cornely, Oliver A.; Burchardt, Alexander; Hachem, Ray; Kontoyiannis, Dimitrios P.; Töpelt, Karin; Courtney, Ronan; Wexler, David; Krishna, Gopal; Martinho, Monika; Corcoran, Gavin; Raad, Issam

doi:10.1128/aac.50.2.658-666.2006

Cited by 264 publications

(238 citation statements)

References 34 publications

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“…Posaconazole has low risk of adverse effects, does not require parenteral administration and hence there is no need for hospitalization. 16 It can also be used as a step down treatment after initial therapy with Amphotericin B. Two case series and more than 20 case reports of successful treatment with Posaconazole have been published and all conclude a significantly good and complete response.…”

Section: Discussionmentioning

confidence: 99%

Management of rhinomaxillary mucormycosis with Posaconazole in immunocompetent patients

Rai

Yadav

Kumar

et al. 2016

Journal of Oral Biology and Craniofacial Research

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Section: Discussionmentioning

confidence: 99%

Management of rhinomaxillary mucormycosis with Posaconazole in immunocompetent patients

Rai

Yadav

Kumar

et al. 2016

Journal of Oral Biology and Craniofacial Research

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“…10 However, there are concerns about achieving reliable therapeutic levels in vivo to treat mucormycosis. 17 Further data from models of neutropenic murine mucormycosis have failed to prove the efficacy of posaconazole as monotherapy. 18 It is therefore not currently recommended as primary treatment for mucormycosis.…”

Section: Discussionmentioning

confidence: 99%

“…17 This allowed us to discharge our patient on long-term posaconazole, to be followed up locally. Effective treatment of mucormycosis with liposomal amphotericin B generally requires doses in excess of 5 mg/ kg (one study found a median of 7 mg/kg).…”

Section: Discussionmentioning

confidence: 99%

Use of posaconazole in the treatment of infective rhinocerebral mucormycosis

et al. 2010

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Introduction: A patients with undiagnosed type II diabetes mellitus presented with infective rhinocerebral mucormycosis.Investigation results: Initial magnetic resonance imaging scans demonstrated an aggressive disease process involving the left orbit and paranasal sinuses. A repeated scan following treatment excluded intracranial spread or recurrence. Pus from the paranasal sinuses grew Rhizopus arrhizus on microbiological culture.Management: Initial treatment comprised intravenous liposomal amphotericin B, intravenous co-amoxiclav and surgical debridement. The patient's diabetes was managed medically. The development of drug-induced transaminitis required a change of medication. The dose of liposomal amphotericin B was reduced, and then titrated back up as the liver function test results improved. Posaconazole was also introduced and the patient was eventually discharged on this alone, as the maximum recommended cumulative dose of liposomal amphotericin B had been reached.Conclusions: Posaconazole may be used effectively in conjunction with surgical debridement in the treatment of patients with infective rhinocerebral mucormycosis who develop hepatotoxic side effects to liposomal amphotericin B. Posaconazole may also allow a reduction in the dose of liposomal amphotericin B, resulting in better tolerance.

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“…Considerando la reducida entidad de las concentraciones plasmáticas y el dato señalado de la fijación a proteínas, es destacable que la concentración plasmática libre resulte muy baja, especialmente en el caso de posaconazol [8,14,31] e itraconazol que, por otra parte, son los fármacos que presentan menor biodisponibilidad.…”

Section: Características Farmacocinéticasunclassified

“…Todos los azoles tienen un volumen de distribución muy elevado que supera, con creces, el contenido de agua corporal que señala de forma clara la afinidad tisular de estos fármacos, y justifica la escasa presencia en plasma [8,14,17,31]. Voriconazol, de forma característica, y que probablemente comparte con los restantes azoles, alcanza una concentración intracelular elevada en polimorfonucleares humanos con una penetración rápida, no saturable e independiente de las condiciones ambientales [5].…”

Section: Características Farmacocinéticasunclassified

Farmacología de los azoles

Azanza

García-Quetglas

Sádaba

2007

Revista Iberoamericana de Micología

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Los azoles presentan características farmacocinéticas diferenciadas, con una absorción oral completa de voriconazol, menor de fluconazol y menos importante y que aumenta con alimentos en el caso de posaconazol e itraconazol. Todos presentan una distribución tisular elevada, que se manifiesta por concentraciones plasmáticas muy reducidas, especialmente en el caso de posaconazol e itraconazol. Estos dos últimos fármacos presentan una fracción libre reducida al circular en plasma unidos a proteínas en proporción elevada. La eliminación es en todos los casos a través de metabolismo con intervención de diversas isoenzimas CYP450, a las que son capaces de inhibir, lo que condiciona una farmacocinética no lineal y un elevado riesgo de interacciones con otros fármacos. Es posible que el parámetro que mejor defina la eficacia sea el AUIC con un valor óptimo de 20. Si esta circunstancia se concreta, debe valorarse el punto de corte para la sensibilidad puesto que algunos de estos fármacos pueden tener dificultades para alcanzar este valor.Farmacología, Posaconazol, Itraconazol, Fluconazol, Voriconazol Pharmacology of azolesAzole antifungals have different pharmacokinetic characteristics: complete oral absorption for Voriconazole, and to a lesser extent for fluconazole. The absorption of posaconazole and itraconazole increases with food intake. All of them have high tissue distribution with low plasma concentrations, especially low in the case of posaconazole and itraconazole. Posaconazole and itraconazole have high plasmatic protein binding and consequently both have a very low free fraction. Elimination of azole antifungals is through a metabolic pathway with CYP450 isoenzymes, and has a non linear pharmacokinetics with a high risk of interation with other drugs since azoles have the ability of CYP450 isoenzymes inhibition. Possibly the parameter that defines more precisely their efficacy is AUIC with an optimum value near 20, although cut-off values must be defined since some azoles may have difficulty to reach this value.Pharmacology, Posaconazole, Itraconazole, Fluconazole, Voriconazole Los azoles forman una familia heterogénea de fár-macos que comparten la presencia de un anillo azólico central y con ello el mecanismo de acción antifúngico, que consiste en la inhibición de la síntesis del ergosterol. Al mismo tiempo los cuatro azoles de interés en el tratamiento de las infecciones sistémicas: fluconazol, itraconazol, voriconazol y posaconazol, presentan diferencias importantes en su estructura, con similitud entre ellos. Estas diferencias en la estructura generan comportamienDirección para correspondencia: Dr. José Ramón Azanza Servicio de Farmacología Clínica Clínica Universitaria de Navarra Avda. Pío XII s/n 31008 -Pamplona Tel.: (+34) 948 296 695 Fax: (+34) 948 296 500 E-mail: jrazanza@unav.es ©2007 Revista Iberoamericana de Micología Apdo. 699, E-48080 Bilbao (Spain) 1130-1406/01/10.00 tos farmacocinéticos distintos que tienen repercusiones notables en el manejo práctico de estos fármacos, a los que se hará refer...

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Pharmacokinetics, Safety, and Efficacy of Posaconazole in Patients with Persistent Febrile Neutropenia or Refractory Invasive Fungal Infection

Cited by 264 publications

References 34 publications

Management of rhinomaxillary mucormycosis with Posaconazole in immunocompetent patients

Management of rhinomaxillary mucormycosis with Posaconazole in immunocompetent patients

Use of posaconazole in the treatment of infective rhinocerebral mucormycosis

Farmacología de los azoles

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