Food for thought: formulating away the food effect – a PEARRL review

O’Shea, Joseph P.; Holm, René; O’Driscoll, Caitriona M.; Griffin, Brendan T.

doi:10.1111/jphp.12957

Cited by 85 publications

(54 citation statements)

References 177 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…22,23 For this reason, the US Food and Drug Administration (FDA) recommends evaluation of bioequivalence following ingestion of a 800-to 1000-kcal meal in which around 50% of the total calories come from fat (as was employed here) to maximize the potential for demonstrating a food effect. 22 In our analysis, food intake seemed to slow the absorption of nifurtimox slightly based on the change in time from dosing to peak plasma concentration (median t max increased from 3 to 4 hours). Total systemic exposure to nifurtimox was also ≈71% greater after food than in a fasted state.…”

Section: Discussionmentioning

confidence: 99%

Biopharmaceutical Characteristics of Nifurtimox Tablets for Age‐ and Body Weight‐Adjusted Dosing in Patients With Chagas Disease

Staß

Feleder²,

García-Bournissen

et al. 2020

Clinical Pharm in Drug Dev

View full text Add to dashboard Cite

Treatment of Chagas disease with nifurtimox requires age-and body weight-adjusted dosing, resulting in complex dosing instructions. Appropriate formulations are needed for precise and compliant dosing, especially in pediatric patients. We characterized the biopharmaceutical features of a standard nifurtimox 120-mg tablet and a 30-mg tablet developed to improve dose accuracy. Two open-label, randomized crossover studies were conducted in adult outpatients with Chagas disease.One study investigated whether 4 × 30-mg tablets and 1 × 120-mg tablet were bioequivalent and whether tablets can be administered as an aqueous slurry without affecting bioavailability. The second study investigated the effect of a high-calorie/high-fat diet versus fasting on the absorption of nifurtimox after a single 4 × 30-mg dose. Interventions were equivalent if the 90% confidence interval (CI) of their least-squares (LS) mean ratios for both AUC 0-tlast and C max were in the range of 80%-125%. The 4 × 30-mg and 1 × 120-mg tablet doses were bioequivalent (AUC 0-tlast : LS mean ratio, 104.7%; 90%CI, 99.1%-110.7%; C max : LS mean ratio, 101.7%; 90%CI, 89.4%-115.6%; n = 24). Exposure when giving the 4 × 30-mg dose as a slurry or as tablets was comparable, with an AUC 0-tlast ratio of 93.2% (84.2%-103.1%; n = 12) and a slightly decreased C max ratio for the slurry of 76.5% (68.8%-85.1%). Food improved the bioavailability of nifurtimox substantially (AUC 0-tlast ratio fed/fasted , 172%; 90%CI, 154%-192%; C max ratio fed/fasted , 168%; 90%CI, 150%-187%). The data indicate that the 30-and 120-mg tablets are suitable for dosing adult and pediatric patients accurately; nifurtimox should be administered under fed conditions.

show abstract

Section: Discussionmentioning

confidence: 99%

Biopharmaceutical Characteristics of Nifurtimox Tablets for Age‐ and Body Weight‐Adjusted Dosing in Patients With Chagas Disease

Staß

Feleder²,

García-Bournissen

et al. 2020

Clinical Pharm in Drug Dev

View full text Add to dashboard Cite

show abstract

“…Food consumption induces dynamic changes in the GI tract (Varum et al, 2013;Abuhelwa et al, 2017;O'Shea et al, 2018) including luminal fluid volume and composition, and patterns of intestinal motility which ultimately affect the transit time of dosage forms (Ofutet et al, 2015;Ibekwe et al, 2008;Fadda et al, 2009;Liu et al, 2009). The understanding of the influence of food on P-gp expression in rodents, its potential difference between sexes and its implications for oral drug delivery are still in its infancy.…”

Section: Introductionmentioning

confidence: 99%

P-glycoprotein expression in the gastrointestinal tract of male and female rats is influenced differently by food

Liu

Yang

Madla

et al. 2018

European Journal of Pharmaceutical Sciences

View full text Add to dashboard Cite

The aim of this study was to explore the influence of food on P-glycoprotein (P-gp) relative expression in both male and female rats, and its effect on intestinal permeation of P-gp substrates (ranitidine and ganciclovir) and a P-gp non-substrate (metformin). The intestine of 12 male and 12 female Wistar rats were excised and segmented into the duodenum, jejunum, ileum and colon. P-gp extracted from each segment was then determined via Western-blotting. In male rats, the relative P-gp expression decreased significantly after food intake in all segments of the intestine except in the duodenum. The most notable change was demonstrated in the colon where relative expression decreased from 1.75 ± 0.36 in the fasted-state to 0.31 ± 0.15 in the fed-state. In female rats, a fundamentally different result was observed. Food ingestion resulted in a significant increase in relative P-gp expression in all regions of the intestine except in the colon. The largest difference was observed in the jejunum of the fed-state female rat intestine where P-gp expression was 1.76 ± 0.95 which was a six-fold increase from the fasted state at 0.34 ± 0.13. Intestinal permeation studies in an Ussing chamber showed that both ganciclovir and ranitidine exhibited a sex difference in intestinal permeability in the fasted-state. No sex differences and food effects were observed on metformin small intestine permeability. The permeability results of the three drugs highly supported that there was a sex-related food effect on P-gp function in the small intestine. In summary, the current study reports stark differences between male and female rats at a physiological level relating to P-gp expression and the influence of food.

show abstract

“…It is believed that in the fed state, liquids and smaller particles (<3-4 mm) such as disintegrated tablets and capsules often empty with food over a time-span which depends largely on the caloric value of the meal. [41] Thus, the gastric emptying time in the fed state can vary and high caloric meals can result in long gastric emptying times. [41][42][43][44][45] In the study of Majumdar et al, the EMEND® capsules were administered to the volunteers 15 minutes following a "standard light breakfast", although no specific information, e.g.…”

Section: Fed Statementioning

confidence: 99%

“…[41] Thus, the gastric emptying time in the fed state can vary and high caloric meals can result in long gastric emptying times. [41][42][43][44][45] In the study of Majumdar et al, the EMEND® capsules were administered to the volunteers 15 minutes following a "standard light breakfast", although no specific information, e.g. the caloric value of the meal, was provided with regard to the nature of the breakfast.…”

Section: Fed Statementioning

confidence: 99%

Combining biorelevant in vitro and in silico tools to simulate and better understand the in vivo performance of a nano-sized formulation of aprepitant in the fasted and fed states

Litou

Patel

Turner

et al. 2019

European Journal of Pharmaceutical Sciences

View full text Add to dashboard Cite

show abstract

Food for thought: formulating away the food effect – a PEARRL review

Cited by 85 publications

References 177 publications

Biopharmaceutical Characteristics of Nifurtimox Tablets for Age‐ and Body Weight‐Adjusted Dosing in Patients With Chagas Disease

Biopharmaceutical Characteristics of Nifurtimox Tablets for Age‐ and Body Weight‐Adjusted Dosing in Patients With Chagas Disease

P-glycoprotein expression in the gastrointestinal tract of male and female rats is influenced differently by food

Combining biorelevant in vitro and in silico tools to simulate and better understand the in vivo performance of a nano-sized formulation of aprepitant in the fasted and fed states

Contact Info

Product

Resources

About