Kukulka Michael, Nudurupati Sai, Perez Maria Claudia
Department of Clinical Pharmacology, Takeda Development Center Americas, Inc., Deerfield, IL, USA.
Department of Analytical Sciences, Takeda Development Center Americas, Inc., Deerfield, IL, USA.
Clin Exp Gastroenterol. 2018 Oct 5;11:381-389. doi: 10.2147/CEG.S138580. eCollection 2018.
To assess the effect of route of administration on the bioavailability of dexlansoprazole 60 mg delayed-release capsule granules.
One open-label, Phase I, single-dose, 3-period crossover study was conducted in healthy adults. The bioavailability of Dexilant (dexlansoprazole) after dexlansoprazole capsule granules were mixed with water and administered via 16 French nasogastric tube or orally via syringe was compared to administration of the intact capsule in the fasted state, swallowed with water. Blood samples were collected before and after dosing to determine dexlansoprazole pharmacokinetic parameter estimates and plasma concentrations.
Similar values for area under the plasma concentration-time curve and observed maximum plasma concentration were achieved when the dexlansoprazole 60 mg capsule was administered as the intact capsule or when the granules were mixed with water and administered via nasogastric tube or orally via syringe. The primary endpoints of maximum plasma concentration and area under the plasma concentration-time curve demonstrated bioequivalence when assessing these alternative routes of administration. Most adverse events were rated as mild and were comparable irrespective of administration route.
Systemic exposure to dexlansoprazole was equivalent regardless of administration route. The dexlansoprazole capsule was well tolerated.
评估给药途径对60毫克右兰索拉唑缓释胶囊颗粒生物利用度的影响。
在健康成年人中进行了一项开放标签、I期、单剂量、3期交叉研究。将右兰索拉唑胶囊颗粒与水混合后通过16号法国鼻胃管给药或通过注射器口服给药后，将右兰索拉唑（Dexilant）的生物利用度与空腹状态下用水吞服完整胶囊的生物利用度进行比较。给药前后采集血样以确定右兰索拉唑的药代动力学参数估计值和血浆浓度。
当60毫克右兰索拉唑胶囊作为完整胶囊给药时，或者当颗粒与水混合并通过鼻胃管给药或通过注射器口服给药时，血浆浓度-时间曲线下面积和观察到的最大血浆浓度的值相似。在评估这些替代给药途径时，最大血浆浓度和血浆浓度-时间曲线下面积的主要终点显示生物等效性。大多数不良事件被评为轻度，且与给药途径无关，情况相似。
无论给药途径如何，右兰索拉唑的全身暴露量是等效的。右兰索拉唑胶囊耐受性良好。
