The Effect of Food on the Single‐Dose Bioavailability and Tolerability of the Highest Marketed Strength of Duloxetine

Abstract

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.

Duloxetine combined with intra-articular injection versus intra-articular injection alone for pain relief in knee osteoarthritis: a study protocol for a randomised controlled trial

“…The patients will be instructed to take the medication with meals. 45 In a retrospective analysis, 46 the use of duloxetine for the treatment of OA of the knee resulted in significant pain relief in both elderly and young groups (p<0.05). However, among the patients in all age groups who did not respond well to duloxetine at 7 weeks, no significant pain relief was found when the dose was increased to 120 mg/day.…”

Duloxetine: An update

“…The pharmacokinetic profile of duloxetine is characterized by its absorption, distribution, metabolism, and excretion: Absorption: Duloxetine is well absorbed after oral administration, with peak plasma concentrations typically occurring 6 hours post-dose. Its bioavailability is approximately 50%, and food does not have a significant impact on its absorption(Eli Lilly and Company, 2004;Rizea-Savu et al, 2020).…”

“…Distribution: It is extensively distributed throughout the body and is highly bound to plasma proteins, mainly albumin and α1acid glycoprotein, which may affect its distribution in various tissues(Eli Lilly and Company, 2004;Rizea-Savu et al, 2020).…”

“…The primary pathway involves cytochrome P450 1A2 (CYP1A2) and cytochrome P450 2D6 (CYP2D6) enzymes, leading to the formation of numerous metabolites, none of which significantly contribute to the drug's therapeutic effects. This extensive metabolism may involve potential interactions with other medications metabolized by the same enzymes(Eli Lilly and Company, 2004;Lobo et al, 2008;Rizea-Savu et al, 2020;Shelton, 2019;Wernicke et al, 2005).…”

The Influence of Caffeine, Celecoxib and Their Combination on Analgesic Processes

“…Caffeine is also contained by many different beverages (tea, energy drinks or soft drinks), foods (chocolate, cocoa), food supplements and medicines. It is very well known that concomitant intake of food [18] or specific beverages (such as grapefruit juice, coffee) [19,20] can have a significant impact on pharmacodynamic or pharmacokinetic properties of various medicinal products and thus the potential for interaction needs to be studied. The effects of coffee or caffeine intake were investigated by various researchers [21][22][23][24].…”