The Pharmacokinetic Exposure to Fexofenadine is Volume‐Dependently Reduced in Healthy Subjects Following Oral Administration With Apple Juice

Abstract

Pharmacokinetic exposures to fexofenadine (FEX) are reduced by apple juice (AJ); however, the relationship between the AJ volume and the degree of AJ‐FEX interaction has not been understood. In this crossover study, 10 healthy subjects received single doses of FEX 60 mg with different volumes (150, 300, and 600 mL) of AJ or water (control). To identify an AJ volume lacking clinically meaningful interaction, we tested a hypothesis that the 90% confidence interval (CI) for geometric mean ratio (GMR) of FEX AUCAJ/AUCwater is contained within a biocomparability bound of 0.5–2.0, with at least one tested volume of AJ. GMR (90% CI) of AUCAJ 150mL/AUCwater, AUCAJ 300mL/AUCwater, and AUCAJ 600mL/AUCwater were 0.903 (0.752–1.085), 0.593 (0.494–0.712), and 0.385 (0.321–0.462), respectively. While a moderate to large AJ‐FEX interaction is caused by a larger volumes of AJ (e.g., 300 to 600 mL), the effect of a small volume (e.g., 150 mL) appears to be not meaningful.

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“…When a single dose of 600 mL apple juice was co-administered with fexofenadine in 10 healthy Japanese subjects, the reduction in fexofenadine exposure was 61.5% and the reduction in exposure dropped to 38.2% when the dose was reduced by half (a single dose of 300 mL apple juice); furthermore, no significant effect (8% decrease) was observed when the dose of co-administered apple juice was reduced even further to 150 mL. 68 Likewise, a similar volumedependent response trend has been observed with grapefruit juice, albeit with a relatively smaller effect compared with apple juice. When decreasing volumes of grapefruit juiceda total of 1200 mL (over 3 h), a single dose of 300 mL, and a single dose of 240 mL of grapefruit juicedwere co-administered with fexofenadine, the AUC of fexofenadine was reduced by approximately 60%, 67,71 40%, [69][70][71] and then only by about 24%, respectively.…”

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“…The sample size was also selected according to the criteria established in the Mexican official standard NOM-177-SSA1-2013 for the administration of a single dose of a drug to healthy volunteers. Feeding variables were controlled to avoid effects from the consumption of food 14 or substances (alcohol or drugs).…”

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“…With respect to extemporaneous preparation, we have also observed trials in which existing dosage forms were modified, and co‐administered foods/beverages interfered with the bioavailability of the active drug compound, resulting in unexpected disposition profiles and, in some cases, failure to satisfy bioequivalence criteria . Through Figure , derived from a study in healthy volunteers, we illustrate the impact of a pediatric dietary staple (apple juice) on the systemic exposure to a medication . Prior to our improved understanding of the impact of drug–nutrient interactions on presystemic drug metabolism and transport, it was not uncommon to encounter pediatric trials permitting concomitant juice administration, and we still see studies that permit flavored beverages (e.g., fruit punch), despite the fact that most contain apple juice as an ingredient.…”

“…Mean plasma concentrations (means ± SD) of fexofenadine ( FEX ) after oral administration of FEX 60 mg with water 600 mL, apple juice ( AJ ) 150 mL, followed by water 450 mL, AJ 300 mL, followed by water 300 mL, and AJ 600 mL. N = 10; image adapted from Luo et al ., https://doi.org/10.1111/cts.12400, is licensed under CC BY‐NC‐ND 4.0. © 2016 The authors.…”

“…7 Through Figure 2, derived from a study in healthy volunteers, we illustrate the impact of a pediatric dietary staple (apple juice) on the systemic exposure to a medication. 12 Prior to our improved understanding of the impact of drug-nutrient interactions on presystemic drug metabolism and transport, it was not uncommon to encounter pediatric trials permitting concomitant juice administration, and we still see studies that permit flavored beverages (e.g., fruit punch), despite the fact that most contain apple juice as an ingredient. Failure to recognize or account for the effect of food and formulation during data capture can introduce added levels of variability, confounding data interpretation and experimental results.…”