三唑类抗真菌新药泊沙康唑的药理基础  

Pharmacokinetic and pharmacodynamic profile of a new triazole antifungal posaconazole

作　　者：孙禾[1,2] 苏欣[1,2] 施毅[1,2] 

机构地区：[1]中国人民解放军第二军医大学南京临床学院 [2]南京军区南京总医院呼吸与危重症医学科,江苏南京210002

出　　处：《中国新药与临床杂志》2012年第11期633-637,共5页Chinese Journal of New Drugs and Clinical Remedies

基　　金：国家自然科学基金-青年科学基金(81000003)

摘　　要：泊沙康唑是第二代三唑类抗真菌药,该口服液通过抑制细胞色素P450依赖的14α-脱甲基酶(CYP51)发挥抗真菌活性。泊沙康唑口服生物利用度变异大,随高脂餐同服吸收率最高,分次给药可增加其生物利用度。在体内蛋白结合率达98%,单次给药后5～8 h血药浓度达峰。泊沙康唑的表观分布容积与给药方案相关,组织分布广泛,穿透力强,口服给药后7～10 d达稳态血药浓度,通过尿苷二磷酸葡萄糖醛酸转移酶途径代谢。泊沙康唑是细胞色素酶CYP3A4的抑制剂,经此通路代谢的药物可受泊沙康唑的影响,血药浓度升高。泊沙康唑主要经消化道清除,清除半衰期20～66 h,口服耐受性良好,不良反应轻微。Posaconazole oral suspension acts by inhibiting cytochrome P450-dependent-14α-demethylase in the biosynthetsis of ergosterol. Since the relative bioavailability is significantly different among regimens, this triazole requires administration with food or a nutritional supplement to assure adequate bioavailability. The extent of protein binding is high （〉 98%）. The time to reach the maximum plasma concentration is about 5 - 8 hours following oral administration of a single dose. Posaconazole has a large mean apparent volume of distribution （Vd/F） influenced by the dosage regimen, suggesting extensive extravascular distribution and penetration into intracellular spaces. The metabolism of posaconazole is mediated predominantly through phase 2 biotransformations via uridine diphosphate glucuronosyhransferase enzyme pathways. As an inhibitor primarily of CYP3A4, plasma concentrations of drugs that are predominantly metabolized by CYP3A4 may be increased by posaconazole. Posaconazole has a median terminal elimination half-life of 20 - 66 hours and is predominantlyeliminated in the feces as unchanged drug. The drug is well tolerated, even in long- term courses. Adverse reactions are generally mild.

关 键 词：三唑类 泊沙康唑 药理学 

分 类 号：R978.5[医药卫生—药品]