Sobue Satoshi, Sekiguchi Kaneo, Shimatani Katsuyoshi, Tan Keith
Department of Clinical Pharmacology, Pfizer Global R&D, Tokyo Laboratories, Pfizer Japan, Inc., Shinjuku Bunka Quint Bldg. 3-22-7, Yoyogi, Shibuya-ku, Tokyo 151-8589, Japan.
J Clin Pharmacol. 2004 Mar;44(3):284-92. doi: 10.1177/0091270003262799.
This was a single blind, placebo-controlled, escalating single-dose, three-period crossover study using two subject cohorts to investigate the safety, tolerability, and pharmacokinetics in healthy male Japanese subjects after intravenous bolus injection of fosfluconazole 50 to 2000 mg, a phosphate prodrug of fluconazole (FLCZ). Fosfluconazole was rapidly converted to FLCZ with only minor amounts excreted in the urine (less than 4% of the dose). Fosfluconazole had a volume of distribution at the higher doses, which was similar to the extracellular volume in man (0.2 L/kg) and was eliminated with a terminal half-life of 1.5 to 2.5 hours. There was apparent dose proportionality in FLCZ pharmacokinetics. C(max) and AUC of FLCZ appeared to increase proportionally with increasing doses of fosfluconazole. There were no apparent dose-dependent trends in t(max), t(1/2), or mean residence time (MRT) of FLCZ. Bolus injection of fosfluconazole was well tolerated at doses of up to 2000 mg in healthy Japanese subjects.
这是一项单盲、安慰剂对照、剂量递增的单剂量、三阶段交叉研究，使用两个受试者队列，旨在研究健康日本男性受试者静脉推注50至2000毫克氟康唑磷酸酯前药氟伏康唑后的安全性、耐受性和药代动力学。氟伏康唑迅速转化为氟康唑，仅有少量经尿液排泄（小于剂量的4%）。高剂量时氟伏康唑的分布容积与人的细胞外液容积（0.2 L/kg）相似，其消除的终末半衰期为1.5至2.5小时。氟康唑的药代动力学具有明显的剂量比例关系。氟康唑的C(max)和AUC似乎随氟伏康唑剂量增加而成比例增加。氟康唑的t(max)、t(1/2)或平均驻留时间（MRT）没有明显的剂量依赖性趋势。在健康日本受试者中，静脉推注高达2000毫克的氟伏康唑耐受性良好。
