Herbrecht R
Département d'Hématologie et d'Oncologie, Hôpital de Hautepierre, Strasbourg, France.
Int J Clin Pract. 2004 Jun;58(6):612-24. doi: 10.1111/j.1368-5031.2004.00167.x.
Posaconazole is a potent, extended-spectrum, investigational triazole anti-fungal that is highly active in pre-clinical in vitro and in vivo models against a wide array of yeasts and moulds, including Aspergillus, Fusarium and Zygomycetes, which are often refractory to polyenes and older azoles. In humans, orally administered posaconazole is absorbed under fed or fasted conditions; however, absorption is significantly improved when it is coadministered with food or liquid nutritional supplements and when the daily dose is divided (into two or four daily doses). Unlike newer azoles, posaconazole is not extensively metabolised by cytochrome P450 (CYP) enzymes and is primarily excreted as parent compound in the faeces. Posaconazole is a CYP3A4 inhibitor, but it does not inhibit the activity of other CYP enzymes. Therefore, in comparison with other azole anti-fungal drugs, posaconazole may have the potential for fewer drug interactions. The pharmacokinetics of posaconazole are not influenced by age, gender or race. Dose adjustments for renal or hepatic impairment do not appear to be indicated based on results from single-dose studies. Preliminary efficacy data from clinical trials are promising. As salvage therapy, posaconazole elicited complete or partial responses in 44 to 75% of patients (N = 97) with invasive fungal infections who were intolerant of, or who had disease refractory to, amphotericin B or itraconazole. In an analysis of patients with aspergillosis, a 42% success rate was observed in the posaconazole arm (n = 107) compared with a 26% success rate in the control arm (n = 86). Importantly, Kaplan-Meier analysis demonstrated a survival benefit in posaconazole-treated patients. Moreover, posaconazole yielded complete or partial responses in 71% of patients with zygomycosis (N = 24). Posaconazole appears to be well tolerated over long-term administration (>1 year) and may represent an important addition to the anti-fungal armamentarium.
泊沙康唑是一种强效、广谱的新型三唑类抗真菌药物，在临床前体外和体内模型中，对多种酵母菌和霉菌具有高度活性，包括曲霉菌、镰刀菌和接合菌，这些真菌通常对多烯类药物和传统唑类药物耐药。在人体中，口服泊沙康唑在进食或禁食条件下均可吸收；然而，与食物或液体营养补充剂同时服用以及将每日剂量分开（分两次或四次服用）时，吸收会显著改善。与新型唑类药物不同，泊沙康唑不会被细胞色素P450（CYP）酶广泛代谢，主要以母体化合物形式经粪便排泄。泊沙康唑是一种CYP3A4抑制剂，但不抑制其他CYP酶的活性。因此，与其他唑类抗真菌药物相比，泊沙康唑发生药物相互作用的可能性可能较小。泊沙康唑的药代动力学不受年龄、性别或种族的影响。根据单剂量研究结果，似乎无需因肾或肝功能损害而调整剂量。临床试验的初步疗效数据很有前景。作为挽救疗法，泊沙康唑使44%至75%（N = 97）对两性霉素B或伊曲康唑不耐受或难治的侵袭性真菌感染患者获得了完全或部分缓解。在一项针对曲霉病患者的分析中，泊沙康唑组（n = 107）的成功率为42%，而对照组（n = 86）的成功率为26%。重要的是，Kaplan-Meier分析显示泊沙康唑治疗的患者有生存获益。此外，泊沙康唑使71%（N = 24）的接合菌病患者获得了完全或部分缓解。长期给药（>1年）时，泊沙康唑似乎耐受性良好，可能是抗真菌药物库中的一个重要补充。
