生物活性

• 靶点	CYP51 IC50:0.25μM

• 描述Cytochrome P450 (P450) enzymes are important in the metabolism of drugs, steroids, fat-soluble vitamins, carcinogens, pesticides, and many other types of chemicals^[3]. Posaconazole is a strong cytochrome P450 3A (CYP3A) inhibitor and commonly used antifungal agent, it has a clear, dose-dependent effect on proliferation of the epimastigote (extracellular) stages, with a minimal inhibitory concentration of 20 nM and an IC50 of 14 nM. Posaconazole has the minimal inhibitory concentration and IC50 values of 3 nM and 0.25 nM. Treatment of infected animals with amiodarone alone reduces parasitemia, increases survival 60 days pi (0% for untreated controls vs 40% for amiodarone-treated animals) and, when given in combination with Posaconazole, delays the development of parasitemia^[4].Posaconazole is active against isolates of Candida and Aspergillus spp. that exhibit resistance to Fluconazole, Voriconazole, and Amphotericin B and is much more active than the other triazoles against zygomycetes^[5].Coadministration of Posaconazole and Boost Plus increases drug exposure compared to the administration of Posaconazole alone in the fasted state. Food, particularly meals high in fat content, significantly increases Posaconazole bioavailability. Systemic exposure to Posaconazole increases 4- and 2.6-fold when it is consumed with a high-fat and nonfat meal, respectively^[6].Posaconazole and Amiodarone may constitute an effective anti-T. cruzi therapy with low side effect^[7]. At twice-daily doses of ≥ 15 mg/kg of body weight, Posaconazole prolongs the survival of the mice and reduces tissue burden^[8].
• 细胞研究
• Cell Data

  Cell Lines	Concentration	Assay Type	Time	Activity Description	Data Sources
  BESM cells	5 μM	Function assay	72 h	Inhibition of sterol 14-alpha-demethylase in Trypanosoma cruzi epimastigotes infected in BESM cells assessed as reduction in episterol content at 5 uM after 72 hrs	20385875
  human hepatocytes	-	Function assay	-	Inhibition of CYP3A4 in human hepatocytes using testosterone as substrate by HPLC/MS/MS method, IC50=0.05 μM	24948565
  mouse 3T3 cells	-	Function assay	-	Antitrypanosomal activity against Trypanosoma cruzi Tulahuen infected in mouse 3T3 cells, EC50=0.3 nM	19875282

• 临床研究

• NCT号	适应症或疾病	临床期	招募状态	预计完成时间	地点
  NCT00811928	-	-	Completed	-	-
  NCT01951430	-	-	Recruiting	December 2018	Italy ... more >> S.O.C. di Ematologia - Azienda Ospedaliera - SS. Antonio e Biagio e Cesare Arrigo Recruiting Alessandria, Italy Contact: Daniela Pietrasanta          Principal Investigator: Daniela Pietrasanta, Dr.          Sub-Investigator: Lorella De Paoli, Dr.          Azienda Ospedaliera - Nuovo Ospedale 'Torrette' Recruiting Ancona, Italy Contact: Antonella Poloni          Principal Investigator: Antonella Poloni, Dr.          Sub-Investigator: Benedetta Costantini, Dr.          UO Ematologia con trapianto-Università degli Studi di Bari Aldo Moro Recruiting Bari, Italy Contact: Giorgina Specchia          Principal Investigator: Giorgina Specchia          Divisione di Ematologia Ospedale A. Perrin Recruiting Brindisi, Italy Contact: Angela Melpignano          Principal Investigator: Angela Melpignano          Sub-Investigator: Gianluca Guaragna          ASL N.8 - Ospedale "A. Businco" - Struttura Complessa di Ematologia e CTMO Recruiting Cagliari, Italy Contact: Anna Angela Di Tucci          Principal Investigator: Anna Angela Di Tucci, Dr.          Sub-Investigator: Graziella Pilo, Dr.          Policlinico di Careggi Recruiting Firenze, Italy Contact: Valeria Santini          Principal Investigator: Valeria Santini          Sub-Investigator: Alessandro Sanna          IRCCS_AOU San Martino-IST-Ematologia 1-Monoblocco 11°piano- lato ponente Recruiting Genova, Italy Contact: Marco Gobbi          Principal Investigator: Marco Gobbi          Sub-Investigator: Maurizio Miglino          ASL Le/1 P.O. Vito Fazzi - U.O. di Ematologia ed UTIE Recruiting Lecce, Italy Contact: Nicola Di Renzo          Principal Investigator: Nicola Di Renzo          Sub-Investigator: Valentina Vezzoli          Azienda Ospedaliera Universitaria - Università degli Studi di Napoli "Federico II" - Facoltà di Medicina e Chirurgia Recruiting Napoli, Italy Contact: Fabrizio Pane          Principal Investigator: Fabrizio Pane          Sub-Investigator: Giuseppe Cerciello          S.C.D.U. Ematologia - DIMECS e Dipartimento Oncologico - Università del Piemonte Orientale Amedeo Avogadro Recruiting Novara, Italy Contact: Gianluca Gaidano          Principal Investigator: Gianluca Gaidano          Sub-Investigator: Monia Lunghi          Università degli Studi di Padova - Ematologia ed Immunologia Clinica Recruiting Padova, Italy Contact: Renato Zambello          Sub-Investigator: Gianni Binotto          Principal Investigator: Renato Zambello          U.O. di Ematologia con trapianto - Centro di Riferimento Regionale per le coagulopatie rare nel bambino e nell'adulto Dipart. Biomedico di Medicina Interna - A.U. Policlinico "Paolo Giaccone" Recruiting Palermo, Italy Contact: Maria Enza Mitra          Principal Investigator: Maria Enza Mitra          Sub-Investigator: Cinzia Maugeri          Cattedra di Ematologia CTMO Università degli Studi di Parma Recruiting Parma, Italy Contact: Monica Crugnola          Principal Investigator: Monica Crugnola          Med. Int. ed Oncologia Medica IRCCS Policlinico S. Matteo Recruiting Pavia, Italy Contact: Rosangela Invernizzi          Principal Investigator: Rosangela Invernizzi, Dr.          Sub-Investigator: Federica Quaglia, Dr.          Div. di Ematologia di Muraglia - CTMO Ospedale San Salvatore Recruiting Pesaro, Italy Contact: Giuseppe Visani          Sub-Investigator: Sara Barulli          Principal Investigator: Giuseppe Visani          U.O. Ematologia Clinica - Azienda USL di Pescara Recruiting Pescara, Italy Contact: Paolo Di Bartolomeo          Principal Investigator: Paolo Di Bartolomeo          Unità Operativa Ematologia e Centro Trapianti - Dipartimento di Oncologia ed Ematologia - AUSL Ospedale di Piacenza Recruiting Piacenza, Italy Contact: Costanza Bosi          Principal Investigator: Costanza Bosi, Dr.          U.O. di Ematologia - Centro Oncologico Basilicata Recruiting Rionero in Vulture, Italy Contact: Pellegrino Musto          Principal Investigator: Pellegrino Musto, Dr.          Sub-Investigator: Oreste Villani, Dr.          Complesso Ospedaliero S. Giovanni Addolorata Recruiting Roma, Italy Contact: Susanna Fennu          Principal Investigator: Susanna Fennu          Sub-Investigator: Stefania Cortese          U.O.C. Ematologia - Ospedale S.Eugenio Recruiting Roma, Italy Contact: Pasquale Niscola          Principal Investigator: Pasquale Niscola          Sub-Investigator: Laura Scaramucci          Università Cattolica del Sacro Cuore - Policlinico A. Gemelli Recruiting Roma, Italy Contact: Livio Pagano, Dr.          Principal Investigator: Livio Pagano, Dr.          Sub-Investigator: Maria Teresa Voso, Dr.          Università degli Studi - Policlinico di Tor Vergata Not yet recruiting Roma, Italy Contact: Adriano Venditti          Principal Investigator: Adriano Venditti, dr.          Sub-Investigator: Luca Maurillo, Dr.          Istituto di Ematologia - IRCCS Ospedale Casa Sollievo della Sofferenza Recruiting S. G. Rotondo, Italy Contact: Nicola Cascavilla          Principal Investigator: Nicola Cascavilla          Sub-Investigator: Grazia Sanpaolo, Dr.          Dipartimento di Oncologia ed Ematologia S.C. Ematologia 2 A.O. Città della Salute e della Scienza di Torino San Giovanni Battista Recruiting Torino, Italy Contact: Bernardino Allione          Sub-Investigator: Stefano D'Ardia          Principal Investigator: Bernardino Allione          Clinica Ematologica-Centro Trapianti e Terapie cellulari Azienda Ospedaliero-Universitaria, Udine Recruiting Udine, Italy Contact: Anna Candoni          Principal Investigator: Anna Candoni          Sub-Investigator: Erica Simeone Collapse <<
  NCT02329808	-	-	Recruiting	December 2018	Netherlands ... more >> Radboud University Medical Center Recruiting Nijmegen, Gelderland, Netherlands Contact: Roger Brüggemann, PharmD PhD       roger.bruggemann@radboudumc.nl    Contact: Lisa Martial, PharmD       lisa.martial@radboudumc.nl    Sub-Investigator: Maroeska Te Loo          Sub-Investigator: Michiel Schreuder          Sub-Investigator: Stefanie Henriet Collapse <<

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• 参考文献

• [1] Chin A, Pergam SA, et al. Evaluation of Posaconazole Serum Concentrations from Delayed-Release Tablets in Patients at High-Risk for Fungal Infections. Antimicrob Agents Chemother. 2017 Jul 31. pii: AAC.00569-17.

  [2] Sansone-Parsons A, Krishna G, et al. Effect of a nutritional supplement on posaconazole pharmacokinetics following oral administration to healthy volunteers. Antimicrob Agents Chemother. 2006 May;50(5):1881-3.

  [3] F Peter Guengerich,et al. Recent Structural Insights into Cytochrome P450 Function. Trends Pharmacol Sci.2016 Aug;37(8):625-640.

  [4] Benaim G, et al. Amiodarone has intrinsic anti-Trypanosoma cruzi activity and acts synergistically with posaconazole. J Med Chem. 2006 Feb 9;49(3):892-9.

  [5] Sabatelli F, et al. In vitro activities of posaconazole, fluconazole, itraconazole, voriconazole, and amphotericin B against a large collection of clinically important molds and yeasts. Antimicrob Agents Chemother. 2006 Jun;50(6):2009-15.

  [6] Sansone-Parsons A, et al. Effect of a nutritional supplement on posaconazole pharmacokinetics following oral administration to healthy volunteers. Antimicrob Agents Chemother. 2006 May;50(5):1881-3.

  [7] Veiga-Santos P, et al. Effects of amiodarone and posaconazole on the growth and ultrastructure of Trypanosoma cruzi. Int J Antimicrob Agents. 2012 Jul;40(1):61-71.

  [8] Sun QN, et al. In vivo activity of posaconazole against Mucor spp. in an immunosuppressed-mouse model. Antimicrob Agents Chemother. 2002 Jul;46(7):2310-2.

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