Effects of Milk or Apple Juice Ingestion on the Pharmacokinetics of Elvitegravir and Cobicistat in Healthy Japanese Male Volunteers: A Randomized, Single‐Dose, Three‐Way Crossover Study

Abstract

Elvitegravir/cobicistat/emtricitabine/tenofovir alafenamide (EVG/COBI/FTC/TAF) is specified in its package insert to be taken with food to obtain sufficient exposure of EVG. It has been reported that a nutritional protein-rich drink shows comparable pharmacokinetics (PK) of EVG to those with a standard breakfast. In this study, the PK profiles of EVG and COBI were evaluated by administration of a single dose of EVG/COBI/FTC/TAF, after ingestion of either a nutritional protein-rich drink, milk, or apple juice. The geometric means for C and AUC of EVG following milk ingestion slightly decreased by 21% and 14%, respectively, and those following apple juice ingestion decreased by 67% and 61%, respectively, compared with a nutritional protein-rich drink. There were no differences in any PK parameters of COBI. Therefore, taking EVG/COBI/FTC/TAF after milk or apple juice ingestion appeared to be not appropriate. However, for plasma trough concentrations (C ), it is known that C is best correlated with the efficacy of EVG. The mean C of EVG after milk ingestion was 620.6 ng/mL, which was more than 10-fold the protein binding-adjusted 95% inhibitory concentration. With all the above considerations, it was concluded that taking EVG/COBI/FTC/TAF with milk could be an option to maintain sufficient plasma concentrations of EVG.

Fexofenadine and Rosuvastatin Pharmacokinetics in Mice with Targeted Disruption of Organic Anion Transporting Polypeptide 2B1

“…For GFJ, the major flavonoid, naringin, is the main constituent involved in the fexofenadine interaction (Bailey et al, 2007). Subsequent studies have found that absorption of other non-or poorly metabolized drugs such as talinolol (Schwarz et al, 2005), celiprolol (Lilja et al, 2003), atenolol (Jeon et al, 2013), aliskiren (Tapaninen et al, 2011) elvitegravir (Yonemura et al, 2018), and levothyroxine (Lilja et al, 2005) are also reduced when taken with fruit juices. The mechanism of fruit juice interactions with nonmetabolized drugs originally focused on OATP1A2 (Dresser et al, 2002), but many investigators are unable to consistently demonstrate that OATP1A2 is expressed in the gastrointestinal tract (Drozdzik et al, 2014).…”

Pharmacokinetic Outcomes of the Interactions of Antiretroviral Agents with Food and Supplements: A Systematic Review and Meta-Analysis

“…While nine studies investigated the effects of food or nutrient supplement on ARV pharmacokinetics [ 12 , 14 , 25 , 27 , 32 , 38 , 42 , 43 , 44 ]. The rest of the studies explored the pharmacokinetic interactions between ARV and vitamins or minerals [ 15 , 29 , 34 , 36 , 37 , 40 ], and dietary supplements [ 28 , 31 , 33 , 35 , 39 , 41 ]. Most studies showed non-significant changes in ARV pharmacokinetic parameters when co-administered with meals.…”

Concurrent administration with multivalent metal cation preparations or polycationic polymer preparations inhibits the absorption of raltegravir via its chelation

“…[ 17,18 ] In addition, in relation to DTG and EVG, there have been reports that concomitant intake of foods or food supplements containing calcium and iron ions by healthy volunteers reduced the values of RAL C max and AUC. [ 19,20 ] However, there have been no previous reports of interaction between the integrase inhibitors and polycationic polymer preparations. Considering the pharmacological mechanism of integrase inhibitors, it is possible that the probable mechanism involved in these interactions may result in the inhibition of absorption, which might occur due to binding between the motif present in the molecular structure of the integrase inhibitor that acts on Mg 2+ in the HIV integrase and ammonium cations in the multivalent metal cation preparations and polycationic polymer preparations.…”