Posaconazole

被引:138
作者
Keating, GM [1 ]
机构
[1] Adis Int Ltd, Auckland, New Zealand
关键词
D O I
10.2165/00003495-200565110-00007
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
Posaconazole is a triazole antifungal agent, administered as an oral suspension, with an extended spectrum of in vitro activity. Posaconazole 800 mg/day demonstrated clinically relevant activity against a range of fungi in patients with invasive fungal infections who were refractory to, or intolerant of, other antifungal therapy in an open-label, multicentre, phase III study (330 patients received posaconazole and 279 patients served as external controls). In aspergillosis, the global response success rate at the end-of-therapy visit.(primary endpoint) was significantly higher in posaconazole recipients than in external controls (42% vs 26%). Posaconazole was also associated with overall success rates of 54% in zygomycosis, 46% in fusariosis, 43% in Pseudallescheria infection, 80% in phaeohyphomycosis and 100% in histoplasmosis. Success rates were 48% in refractory candidiasis, 69% in refractory coccidioidomycosis, 48% in refractory cryptococcal infection and 82% in refractory chromoblastomycosis or mycetoma. Posaconazole also demonstrated potential in febrile neutropenia in an open-label phase 11 study (success rate of 81% 7 days after the end of treatment). In a noncomparative, multicentre, phase III study in patients with advanced HIV infection who had azole-refractory oropharyngeal and/or oesophageal candidiasis, posaconazole 400 or 800 mg/day resulted in a clinical response in 132 of 176 patients (75%). Oral posaconazole suspension was generally well tolerated in patients with invasive fungal infections, including patients who received treatment for > 1 year.
引用
收藏
页码:1553 / 1567
页数:15
相关论文
共 100 条
[61]   Mutations in Aspergillus fumigatus resulting in reduced susceptibility to posaconazole appear to be restricted to a single amino acid in the cytochrome p450 14α-demethylase [J].
Mann, PA ;
Parmegiani, RM ;
Wei, SQ ;
Mendrick, CA ;
Li, X ;
Loebenberg, D ;
DiDomenico, B ;
Hare, RS ;
Walker, SS ;
McNicholas, PA .
ANTIMICROBIAL AGENTS AND CHEMOTHERAPY, 2003, 47 (02) :577-581
[62]  
MANN PA, 2004, 44 INT C ANT AG CHEM
[63]   Treatment of Scedosporium apiospermum brain abscesses with posaconazole [J].
Mellinghoff, IK ;
Winston, DJ ;
Mukwaya, G ;
Schiller, GJ .
CLINICAL INFECTIOUS DISEASES, 2002, 34 (12) :1648-1650
[64]   Azole cross-resistance in Aspergillus fumigatus [J].
Mosquera, J ;
Denning, DW .
ANTIMICROBIAL AGENTS AND CHEMOTHERAPY, 2002, 46 (02) :556-557
[65]   Posaconazole is a potent inhibitor of sterol 14α-demethylation in yeasts and molds [J].
Munayyer, HK ;
Mann, PA ;
Chau, AS ;
Yarosh-Tomaine, T ;
Greene, JR ;
Hare, RS ;
Heimark, L ;
Palermo, RE ;
Loebenberg, D ;
McNicholas, PM .
ANTIMICROBIAL AGENTS AND CHEMOTHERAPY, 2004, 48 (10) :3690-3696
[66]   Activity of posaconazole combined with amphotericin B against Aspergillus flavus infection in mice:: Comparative studies in two laboratories [J].
Najvar, LK ;
Cacciapuoti, A ;
Hernandez, S ;
Halpern, J ;
Bocanegra, R ;
Gurnani, M ;
Menzel, F ;
Loebenberg, D ;
Graybill, JR .
ANTIMICROBIAL AGENTS AND CHEMOTHERAPY, 2004, 48 (03) :758-764
[67]   Case study:: Posaconazole treatment of disseminated phaeohyphomycosis due to Exophiala spinifera [J].
Negroni, R ;
Helou, SH ;
Petri, N ;
Robles, AM ;
Arechavala, A ;
Bianchi, MH .
CLINICAL INFECTIOUS DISEASES, 2004, 38 (03) :E15-E20
[68]  
NEGRONI R, 2003, 43 INT C ANT AG CHEM
[69]   Efficacy of SCH-56592 in a temporarily neutropenic murine model of invasive aspergillosis with an itraconazole-susceptible and an itraconazole-resistant isolate of Aspergillus fumigatus [J].
Oakley, KL ;
Morrissey, G ;
Denning, DW .
ANTIMICROBIAL AGENTS AND CHEMOTHERAPY, 1997, 41 (07) :1504-1507
[70]  
OLIVEIRA ER, 2004, FOCUS FUNGAL INFECT, V14