3S-Pharmacological Consultation & Research GmbH, Harpstedt, Germany.
3S-Pharmacological Consultation & Res. SRL, Bucharest, Romania.
Clin Pharmacol Drug Dev. 2020 Oct;9(7):797-804. doi: 10.1002/cpdd.759. Epub 2019 Dec 2.
Duloxetine is a combined serotonin and norepinephrine reuptake inhibitor indicated in adults for the treatment of major depressive disorder, diabetic peripheral neuropathic pain, and generalized anxiety disorder. The aim of these studies was to evaluate the effect of food on the pharmacokinetics and safety of duloxetine 60-mg gastroresistant hard capsules following single-dose administration. The data were obtained from 2 phase 1 bioequivalence studies, 1 in a fasting state and the other under fed conditions. Both studies have shown that, when administered as a single dose in the same prandial state, the test and reference duloxetine treatments were bioequivalent and exhibited similar safety profiles. The mean fed and fasting pharmacokinetic parameters and drug-related adverse events from the 2 studies were compared in order to assess the effect of food on the duloxetine bioavailability and respectively, tolerability. Administration of duloxetine in fed conditions increased peak plasma concentration by up to 30% and delayed mean time to peak concentration by an average of 1.15 hours while having an insignificant effect on extent of absorption (area under the plasma concentration-time curve in fed state within ±6% as compared with fasting conditions). Even though peak plasma levels were substantially higher in the fed state, there was no negative impact on the drug's safety profile. Actually, administration with food resulted in a lower average number of adverse events per single dose exposure. The negligible variation in overall systemic exposure suggests that efficacy remains unchanged irrespective of administration conditions; however, a better tolerability of the 60-mg dose is expected when the drug is taken with food.
度洛西汀是一种同时抑制 5-羟色胺和去甲肾上腺素再摄取的药物，适用于治疗成人重度抑郁症、糖尿病外周神经性疼痛和广泛性焦虑症。这些研究旨在评估食物对单次给予 60 毫克度洛西汀肠溶胶囊后度洛西汀药代动力学和安全性的影响。该数据来自 2 项 1 期生物等效性研究，1 项为禁食状态，另 1 项为进食状态。这两项研究均表明，在相同的进食状态下单次给药时，受试制剂和参比制剂度洛西汀具有生物等效性，且安全性特征相似。为了评估食物对度洛西汀生物利用度和耐受性的影响，比较了这两项研究中进食和禁食状态下的平均药代动力学参数和与药物相关的不良事件。进食状态下给予度洛西汀可使血浆峰浓度增加 30%左右，平均达峰时间延迟 1.15 小时，而对吸收程度（与禁食状态相比，进食状态下的 AUC0-t 在±6%范围内）无显著影响。尽管进食状态下的血浆峰浓度显著升高，但对药物的安全性无负面影响。实际上，与单次给药相比，进食时不良事件的平均发生次数更少。总体全身暴露的微小变化表明，无论给药条件如何，疗效均保持不变；然而，与空腹相比，进食时度洛西汀 60 毫克剂量的耐受性预计会更好。
