Division of Infectious Diseases and Tropical Medicine, Department of Internal Medicine, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan.
Ther Drug Monit. 2013 Apr;35(2):223-7. doi: 10.1097/FTD.0b013e3182818a56.
The pharmacokinetic parameters of a single 400-mg oral dose of posaconazole suspension, administered under fasting and fed conditions, were compared in healthy male Taiwanese volunteers.
After an overnight fast, 16 subjects received a single oral dose of posaconazole suspension (400 mg) under fasting conditions or immediately after a normal-fat (700-800 calories, 30% fat) or high-fat breakfast meal (800-1000 calories, 50% fat). The treatments were administered as per the 3 × 6 Williams square design, with a 1-week washout phase between treatments. Blood samples were drawn at predetermined time points (0, 1, 2, 3, 4, 4.5, 5, 5.5, 6, 8, 10, 12, 24, 48, 72, 96, and 120 hours). All plasma concentrations of posaconazole were measured by high-performance liquid chromatography. The observed maximum plasma concentration (C max), area under the plasma concentration-time curve (AUC 0-t and AUC 0-∞), time to reach C max (t max), and plasma half-life (t 1/2) were assessed.
Fourteen subjects completed the study; 2 subjects withdrew because of adverse events. Thirteen subjects were included in the pharmacokinetic analysis. Sixteen subjects were included in the safety analysis. The mean posaconazole C max, AUC 0-t, and AUC 0-∞ values were significantly lower under fasting conditions than after a normal- or a high-fat meal. The mean C max values under fasting, normal-fat, and high-fat conditions were 279.00 ± 123.32 ng/mL, 662.46 ± 251.02 ng/mL, and 608.38 ± 183.22 ng/mL, respectively (P < 0.0001); the mean AUC 0-t values under each condition were 6828.56 ± 3349.12 ng · mL(-1) · h(-1), 20,629.84 ± 8346.45 ng · mL(-1) · h(-1), and 20,741.09 ± 7681.02 ng · mL(-1) · h(-1), respectively (P < 0.0001); and the mean AUC 0-∞ values under each condition were 7304.72 ± 3444.54 ng · mL(-1) · h(-1), 21,326.65 ± 8495.01 ng · mL(-1) · h(-1), and 21,626.08 ± 8193.31 ng · mL · h(-1), respectively (P < 0.0001). The mean t max value was significantly shorter at 3.15 hours under fasting conditions than at 4.88 hours after normal- or high-fat meals (P = 0.0176). The mean t 1/2 values were 22.0, 20.8, and 22.0 hours, respectively.
The posaconazole AUC increased by approximately 3-fold, C max by 2.2-fold, and t max by 1.5-fold when healthy Taiwanese subjects were administered the drug with food compared with under fasting conditions. These parameters were similar when the drug was administered with either a normal- or high-fat meal.
比较健康台湾男性志愿者空腹和进食条件下单次口服 400 毫克泊沙康唑混悬剂的药代动力学参数。
受试者禁食一夜后，空腹或进食标准脂肪（700-800 卡路里，30%脂肪）或高脂肪早餐（800-1000 卡路里，50%脂肪）后单次口服泊沙康唑混悬剂（400mg）。按照 3×6 威廉姆斯方设计进行治疗，每种治疗之间有 1 周的洗脱期。在预定时间点（0、1、2、3、4、4.5、5、5.5、6、8、10、12、24、48、72、96 和 120 小时）抽取血样。所有泊沙康唑的血浆浓度均采用高效液相色谱法测定。评估观察到的最大血浆浓度（C max）、血浆浓度-时间曲线下面积（AUC 0-t 和 AUC 0-∞）、达峰时间（t max）和血浆半衰期（t 1/2）。
14 名受试者完成了研究；2 名受试者因不良事件退出。13 名受试者纳入药代动力学分析。16 名受试者纳入安全性分析。与空腹相比，进食标准脂肪或高脂肪餐时，泊沙康唑的 C max、AUC 0-t 和 AUC 0-∞ 值均显著降低。空腹、标准脂肪和高脂肪条件下的平均 C max 值分别为 279.00±123.32ng/mL、662.46±251.02ng/mL 和 608.38±183.22ng/mL（P<0.0001）；每种条件下的平均 AUC 0-t 值分别为 6828.56±3349.12ng·mL-1·h-1、20629.84±8346.45ng·mL-1·h-1 和 20741.09±7681.02ng·mL-1·h-1（P<0.0001）；每种条件下的平均 AUC 0-∞值分别为 7304.72±3444.54ng·mL-1·h-1、21326.65±8495.01ng·mL-1·h-1 和 21626.08±8193.31ng·mL-1·h-1（P<0.0001）。与进食标准脂肪或高脂肪餐相比，空腹时 t max 均值显著缩短至 3.15 小时（P=0.0176）。平均 t 1/2 值分别为 22.0、20.8 和 22.0 小时。
与空腹相比，当健康台湾受试者进食时，泊沙康唑 AUC 增加约 3 倍，C max 增加 2.2 倍，t max 增加 1.5 倍。当与标准脂肪或高脂肪餐一起给药时，这些参数相似。
