Carrigan P J, Brinker D R, Cavanaugh J H, Lamm J E, Cloyd J C
Pharmaceutical Products Division, Abbott Laboratories, North Chicago, Illinois 60064.
J Clin Pharmacol. 1990 Aug;30(8):743-7. doi: 10.1002/j.1552-4604.1990.tb03637.x.
To determine the absorption characteristics of a new dosage form of divalproex sodium consisting of coated particles in a pull-apart capsule (Depakote Sprinkle, Abbott Laboratories, North Chicago, IL), two absorption studies were conducted in adult volunteers. Ten fasting men participated in a single-dose, crossover study comparing absorption from Sprinkle capsules versus enteric-coated tablets (study 1). Eleven men participated in a multidose study (study 2) in which Sprinkle capsules or enteric-coated tablets were given once every 24 hours for three doses under fasting and nonfasting conditions. In study 1, the extent of absorption from Sprinkle capsules equalled that from enteric-coated tablets. Compared to enteric-coated tablets, Sprinkle capsules had earlier absorption onset, 1 versus 2.6 hours (P less than .05), slightly slower absorption rate, time to reach peak (tmax) of 4.0 versus 3.4 hours (P less than .1), and lower maximum peak plasma drug concentration (Cmax), 20.7 versus 25.9 mcg/mL (P less than .05). In study 2, food intake did not affect onset or extent of absorption nor maximum concentration, but did slow rate of absorption. Time to reach peak concentration was 2.7 hours for tablet (fasting), 3.3 hours for capsule (fasting), and 4.8 hours for capsule (nonfasting) (P less than .05). Intrasubject absorption performance from the three doses was highly consistent, regardless of food intake. These data indicate that Sprinkle capsules possess desirable absorption characteristics in a form that makes ingestion easier for patients who have difficulty taking other valproate dosage forms.
为确定由拉开式胶囊（德巴金速溶片，雅培实验室，伊利诺伊州北芝加哥）中的包衣颗粒组成的丙戊酸钠新剂型的吸收特性，在成年志愿者中进行了两项吸收研究。10名空腹男性参与了一项单剂量交叉研究，比较了速溶片胶囊与肠溶衣片的吸收情况（研究1）。11名男性参与了一项多剂量研究（研究2），在禁食和非禁食条件下，每24小时服用一次速溶片胶囊或肠溶衣片，共服用三剂。在研究1中，速溶片胶囊的吸收程度与肠溶衣片相当。与肠溶衣片相比，速溶片胶囊的吸收起始时间更早，分别为1小时和2.6小时（P<0.05），吸收速度略慢，达峰时间（tmax）分别为4.0小时和3.4小时（P<0.1），最大血浆药物浓度（Cmax）更低，分别为20.7和25.9 mcg/mL（P<0.05）。在研究2中，食物摄入不影响吸收起始时间或程度以及最大浓度，但会减慢吸收速度。片剂（禁食）的达峰时间为2.7小时，胶囊（禁食）为3.3小时，胶囊（非禁食）为4.8小时（P<0.05）。无论食物摄入情况如何，三剂药物的受试者内吸收性能高度一致。这些数据表明，速溶片胶囊具有理想的吸收特性，其剂型使难以服用其他丙戊酸盐剂型的患者更容易吞服。
