Padhi Desmond, Salfi Margaret, Harris Robert Z
Department of Early Development/Medical Sciences, Amgen Inc. Thousand Oaks, CA 91320, USA.
Am J Ther. 2007 May-Jun;14(3):235-40. doi: 10.1097/01.mjt.0000212703.71625.26.
Cinacalcet HCl reduces iPTH, serum calcium, serum phosphorus, and the calcium-phosphorus product in patients with chronic kidney disease and secondary hyperparathyroidism who are receiving dialysis, and reduces elevated serum calcium associated with primary hyperparathyroidism and parathyroid carcinoma. Cinacalcet is administered orally, and thus concomitant administration with food may affect its bioavailability. The objective of this study was to examine the effect of fat and caloric intake on cinacalcet exposure. This phase 1, randomized, open-label, single-dose, 3-period, 3-treatment, 6-sequence crossover study enrolled 30 healthy subjects (19 men, 11 women) to receive a single oral dose of cinacalcet HCl (Sensipar/Mimpara; Amgen Inc. Thousand Oaks, CA) (90 mg) on 3 separate occasions: following a high-fat, high-caloric meal, a low-fat, low-caloric meal, and a 10-hour fast. Blood samples were obtained predose and up to 72 hours postdose for pharmacokinetic (AUCinfinity, Cmax) and safety evaluations. Twenty-nine subjects completed all the 3 treatment conditions. The mean (90% confidence intervals) AUCinfinity following high- and low-fat meals was increased by 68 (48 to 89)% and 50 (33 to 70)%, respectively, relative to fasting. The difference in mean AUCinfinity between high- and low-fat meals was small [12 (9.9-26)%]. The mean tmax of cinacalcet was prolonged in fasting subjects (6 h) in relation to high-fat (4 h) and low-fat (3.5 h) fed subjects. The mean t1/2beta was similar between treatment conditions. Adverse events (AE) were observed at a similar frequency across the treatment conditions [high fat (34%), low fat (23%), and fasting (31%)]; the type of AE did not differ among the treatment conditions. The most common treatment-related AEs were headache 6/30 (20%), nausea 5/30 (17%), and dyspepsia 4/30 (13%) subjects. Administration of cinacalcet with either high- or low-fat meals results in significant increases in exposure, relative to administration under fasting conditions. However, the small differences observed in exposure following the ingestion of the different types of meals suggest that although food has a significant effect, the type of food does not. The observed effect supports the labeling statement that cinacalcet be taken with food, or shortly after a meal.
盐酸西那卡塞可降低接受透析的慢性肾脏病和继发性甲状旁腺功能亢进患者的血iPTH、血清钙、血清磷以及钙磷乘积，并降低与原发性甲状旁腺功能亢进和甲状旁腺癌相关的血清钙升高。西那卡塞通过口服给药，因此与食物同时服用可能会影响其生物利用度。本研究的目的是考察脂肪和热量摄入对西那卡塞暴露量的影响。这项1期随机、开放标签、单剂量、3周期、3治疗、6序列交叉研究纳入了30名健康受试者（19名男性，11名女性），在3个不同场合分别单次口服一剂盐酸西那卡塞（Sensipar/Mimpara；安进公司，加利福尼亚州千橡市）（90 mg）：高脂高热量餐后、低脂低热量餐后以及禁食10小时后。在给药前和给药后长达72小时采集血样进行药代动力学（AUCinf、Cmax）和安全性评估。29名受试者完成了所有3种治疗情况。与禁食相比，高脂餐和低脂餐后的平均（90%置信区间）AUCinf分别增加了68%（48%至89%）和50%（33%至70%）。高脂餐和低脂餐之间平均AUCinf的差异较小[12%（9.9% - 26%）]。西那卡塞的平均tmax在禁食受试者中（6小时）比高脂（4小时）和低脂（3.5小时）进食受试者延长。各治疗情况之间的平均t1/2β相似。各治疗情况中不良事件（AE）的观察频率相似[高脂（34%）、低脂（23%）和禁食（31%）]；治疗情况之间AE的类型无差异。最常见的与治疗相关的AE是头痛6/30（20%）、恶心5/30（17%）和消化不良4/30（13%）的受试者。与禁食条件下给药相比，西那卡塞与高脂或低脂餐同时服用均导致暴露量显著增加。然而，摄入不同类型餐食后观察到的暴露量差异较小，这表明尽管食物有显著影响，但食物类型并无影响。观察到的结果支持了西那卡塞应与食物同服或餐后不久服用的标签声明。
