Kukulka Michael, Nudurupati Sai, Perez Maria Claudia
Takeda Development Center Americas, Inc., Deerfield, IL, USA.
Clin Exp Gastroenterol. 2017 Feb 17;10:47-56. doi: 10.2147/CEG.S121129. eCollection 2017.
Dexlansoprazole is a proton pump inhibitor (PPI) approved for use in dual delayed-release capsule and orally disintegrating tablet (ODT) formulations.
To assess effects of food, water, and route of administration on the bioavailability of dexlansoprazole 30-mg ODT.
Two separate open-label, phase 1, single-dose crossover studies were conducted in healthy adults. In study 1, pharmacokinetic parameters were analyzed in participants receiving dexlansoprazole ODT in a fed or fasted state with and without water. In study 2, the bioavailability of dexlansoprazole after administration via oral syringe or nasogastric (NG) tube, or after swallowing intact with water was compared to ODT administration in the fasted state, swallowed without water. Blood samples for determining dexlansoprazole plasma concentrations and pharmacokinetic parameter estimates were collected before and after dosing.
Equivalent values for area under the plasma concentration-time curve (AUC) were observed in the fed and fasted states, but the maximum observed plasma concentration (C) was 38% lower in the fed state; therefore, bioequivalence was not achieved. A water rinse following standard ODT administration decreased dexlansoprazole bioavailability, with lower C and AUC values than when ODT was administered without a water rinse. Bioequivalence was demonstrated when comparing the alternative routes of administration, including via oral syringe or NG tube with standard ODT administration. Unlike with a water rinse, bioequivalence to standard ODT administration (i.e., without water) was demonstrated when swallowing the ODT intact with water. Rates of adverse events were comparable irrespective of administration route in the fasted state (6.7%-9.3%) and were 12% higher in the fed state than in the fasted state.
The AUC from the dexlansoprazole ODT was equivalent when administered in the fed and fasted states. Equivalent systemic exposure to dexlansoprazole was achieved regardless of the administration route.
右兰索拉唑是一种质子泵抑制剂（PPI），已被批准用于双延迟释放胶囊和口腔崩解片（ODT）剂型。
评估食物、水和给药途径对30毫克右兰索拉唑口腔崩解片生物利用度的影响。
在健康成年人中进行了两项独立的开放标签1期单剂量交叉研究。在研究1中，分析了在进食或禁食状态下，有水或无水时接受右兰索拉唑口腔崩解片的参与者的药代动力学参数。在研究2中，将通过口服注射器或鼻胃管给药后，或完整用水吞咽后右兰索拉唑的生物利用度与禁食状态下无水吞咽的口腔崩解片给药进行比较。在给药前后采集用于测定右兰索拉唑血浆浓度和药代动力学参数估计值的血样。
在进食和禁食状态下观察到血浆浓度-时间曲线下面积（AUC）的等效值，但进食状态下观察到的最大血浆浓度（C）低38%；因此，未实现生物等效性。标准口腔崩解片给药后用水冲洗会降低右兰索拉唑的生物利用度，其C和AUC值低于未用水冲洗而给药口腔崩解片时。比较包括通过口服注射器或鼻胃管给药与标准口腔崩解片给药在内的替代给药途径时，证明了生物等效性。与用水冲洗不同，完整用水吞咽口腔崩解片时证明与标准口腔崩解片给药（即无水）具有生物等效性。无论在禁食状态下的给药途径如何，不良事件发生率相当（6.7%-9.3%），且进食状态下比禁食状态高12%。
右兰索拉唑口腔崩解片在进食和禁食状态下给药时AUC等效。无论给药途径如何，右兰索拉唑的全身暴露量相当。
