The efficacy of the selective serotonin and norepinephrine reuptake inhibitor antidepressant duloxetine does not differ when patients with depression take it on an empty stomach or following a meal, according to study results published in Clinical Pharmacology in Drug Development. However, researchers found that the medication is better tolerated when taken with food.
Romanian researchers conducted two phase 1 studies evaluating the effect of food on the pharmacokinetic parameters and safety of duloxetine 60-mg gastro-resistant hard capsules following single-dose administration. After at least 8 hours of overnight fasting, patients in the fasting study took a single 60-mg oral dose of name brand or generic duloxetine with water. The conditions of the second study only differed in that patients received the dose exactly 30 minutes after they started eating breakfast. The fasting study comprised 72 patients, 71 of whom received at least 1 dose of study medication and were included in the safety population; 66 completed the clinical part of the trial and were included in the per-protocol pharmacokinetic population. In the study evaluating the effect of food on duloxetine, 44 patients were enrolled, of whom 42 were included in the per-protocol pharmacokinetic population and all 42 were included in the safety population.
In patients who took the medication with food, the pharmacokinetic results showed that peak serum concentration increased by up to 30 and time to reach peak plasma concentration was increased by 20%. The average delay in reaching peak plasma levels was 1.15 hours for both generic and brand name medication when taken with food. Overall, there was no statistically relevant difference in systemic exposure, which suggests that the presence of food was not linked to drug efficacy; however, the extent of absorption was not influenced significantly (fed state within ±6% for absorption compared with fasting conditions).
A larger percentage of the fasting group experienced adverse effects compared with patients who received their doses with food. A total of 49.3% of fasting patients reported gastrointestinal disorders vs 9.1% of the fed population, which was followed by 26.8% with nervous system disorders vs 6.8%, respectively. Based on the average number of adverse events per single-dose, researchers concluded that duloxetine is better tolerated when administered after a meal vs during prolonged fasting. They added that prolonged fasting itself could not be excluded as a contributing factor for adverse effects, especially those of a gastric nature.
“Even though the peak plasma levels were substantially higher in the fed state, food increased duloxetine’s tolerability,” the researchers wrote. “The negligible variation in overall systemic exposure suggests that efficacy remains unchanged irrespective of administration conditions; however, a better tolerability is expected for the 60-mg dose if taken with food.”
Rizea-Savu S, Duna SN, Ghita A, Iordachescu A, Chirila M. The effect of food on the single-dose bioavailability and tolerability of the highest marketed strength of duloxetine [published online December 2, 2019]. Clin Pharmacol Drug Dev. doi:10.1002/cpdd.759