Center for Infectious Diseases Research and Experimental Therapeutics, Baylor Research Institute, Baylor University Medical Center, Dallas, Texas.
Clin Infect Dis. 2015 Dec 1;61 Suppl 6:S635-42. doi: 10.1093/cid/civ715.
The time the earth takes to rotate its axis (the day) has dictated how often pharmaceutical compounds are dosed. The scientific link between the 2 events is materia medica arcana. As an example, in the treatment of invasive candidiasis, antifungal therapy with intravenous micafungin is dosed daily. A literature review revealed population pharmacokinetic analyses, in vivo pharmacokinetics/pharmacodynamics studies, and maximum-tolerated-dose studies of micafungin that examined optimal micafungin dosing strategies. The half-life of micafungin in patient blood was 14 hours in several studies, but was even longer in different organs, so that the concentration will persist above minimum inhibitory concentrations of Candida species for several days. Studies in mice and rabbits with persistent neutropenia and disseminated candidiasis, otherwise fatal, demonstrated that a single large dose of micafungin could clear disseminated candidiasis, even though the micafungin half-life in such animals is shorter than in humans. Human pharmacokinetics/pharmacodynamics studies confirmed this link between micafungin efficacy and the ratio of the area under the concentration-time curve, and the optimal exposures initially identified in neutropenic animals. Maximum tolerated dose studies have demonstrated safety of 900 mg administered daily for several weeks, whereas case reports demonstrate efficacy and safety of single 1400-mg doses. Thus, a single dose of micafungin, or 2 such doses within a few days of each other, is not only logical, but might even lead to faster clearance of Candida.
地球自转（一天）的时间决定了药物化合物的给药频率。这两个事件之间的科学联系是药物的神秘特性。例如，在侵袭性念珠菌病的治疗中，静脉注射米卡芬净的抗真菌治疗每天给药一次。文献综述揭示了米卡芬净的群体药代动力学分析、体内药代动力学/药效学研究和最大耐受剂量研究，这些研究检查了米卡芬净的最佳给药策略。在几项研究中，米卡芬净在患者血液中的半衰期为 14 小时，但在不同器官中甚至更长，因此浓度将持续数天高于念珠菌属的最低抑菌浓度。在持续中性粒细胞减少和播散性念珠菌病（否则致命）的小鼠和兔中进行的研究表明，单次大剂量米卡芬净可清除播散性念珠菌病，尽管此类动物中的米卡芬净半衰期短于人类。人体药代动力学/药效学研究证实了米卡芬净疗效与浓度-时间曲线下面积比值之间的这种联系，以及最初在中性粒细胞减少动物中确定的最佳暴露量。最大耐受剂量研究表明，每天给予 900mg 数周是安全的，而病例报告表明单次给予 1400mg 剂量的疗效和安全性。因此，米卡芬净的单次剂量或彼此相隔几天的 2 次剂量不仅是合理的，甚至可能导致念珠菌更快清除。
