Wiederhold Nathan P
Departments of Pathology and Medicine/Infectious Diseases, University of Texas Health Science Center at San Antonio, South Texas Reference Laboratories, San Antonio, TX, USA.
Clin Pharmacol. 2015 Dec 23;8:1-8. doi: 10.2147/CPAA.S60933. eCollection 2016.
Posaconazole is a broad-spectrum triazole antifungal agent with potent activity against various pathogenic fungi, including yeast and moulds. Clinical studies have demonstrated that this agent is efficacious as prophylaxis against invasive fungal infections in patients at high risk, and may also be useful as salvage therapy against invasive aspergillosis and mucormycosis. However, the bioavailability of posaconazole following administration by oral suspension, which was the only formulation clinically available for many years, is highly variable and negatively influenced by several factors. Because of this, many patients had subtherapeutic or undetectable posaconazole levels when the oral suspension was used. To overcome this limitation, a delayed-release tablet was developed and is now available for clinical use. Hot-melt extrusion technology is used to combine a pH-sensitive polymer with posaconazole to produce a formulation that releases the drug in the elevated pH of the intestine where absorption occurs rather than in the low-pH environment of the stomach. This results in enhanced bioavailability and increased posaconazole exposure. Studies in healthy volunteers have demonstrated significantly higher and more consistent exposures with the tablet formulation compared to the oral suspension. In addition, pharmacokinetic parameters following administration of the tablets were not significantly affected by medications that raise gastric pH or increase gastric motility, and the tablets could also be administered without regard to food. Similar results have also been found in patients at high risk for invasive fungal infections who have received posaconazole tablets. The tablet formulation also appears to be well tolerated to date, although data regarding clinical efficacy are needed.
泊沙康唑是一种广谱三唑类抗真菌药物，对包括酵母菌和霉菌在内的多种致病真菌具有强大活性。临床研究表明，该药物作为高危患者侵袭性真菌感染的预防用药有效，也可能作为侵袭性曲霉病和毛霉病的挽救治疗药物。然而，多年来临床上唯一可用的剂型——口服混悬液给药后泊沙康唑的生物利用度高度可变，且受到多种因素的负面影响。因此，使用口服混悬液时，许多患者的泊沙康唑水平低于治疗浓度或检测不到。为克服这一局限性，研发了一种缓释片，现已可供临床使用。热熔挤出技术用于将一种pH敏感聚合物与泊沙康唑结合，以生产一种制剂，该制剂在吸收发生的肠道较高pH环境而非胃的低pH环境中释放药物。这导致生物利用度提高，泊沙康唑暴露增加。健康志愿者的研究表明，与口服混悬液相比，片剂制剂的暴露量显著更高且更一致。此外，服用片剂后的药代动力学参数不受提高胃pH值或增加胃动力的药物显著影响，片剂也可以与食物无关地给药。在接受泊沙康唑片剂的侵袭性真菌感染高危患者中也发现了类似结果。尽管需要有关临床疗效的数据，但迄今为止片剂制剂似乎耐受性良好。
