The development of orally administered therapeutics seems like a straightforward endeavour until basic biological processes, such as eating, crashes the party. A key initial step when developing orally administered drugs is to understand the potential effect food can have on the pharmacokinetic profile.

The effect of food on drug bioavailability is determined by Attentive Scientists after comparing fasted and fed exposure levels and identifying changes in key pharmacokinetic parameters such as Cmax, Tmax and AUC ratios.

Attentive Science will provide expert guidan​ce throughout the development of your program to ensure the generation of appropriate study designs to answer the key questions related to food effects.

Fundamentals of Food Interaction and Oral Drug Absorption

When medications are ingested, they navigate a complex journey through the gastrointestinal (GI) tract to reach their target site within the body. This journey begins as the drug dissolves in the stomach or intestines, where it is then absorbed into the bloodstream. The extent and rate of absorption can vary widely among different drugs, and several factors contribute to this variability. One crucial factor that researchers have long recognized is the influence of dietary constituents on drug absorption. A recent study demonstrated that compounds that show increased absorption in the fed state had higher logP and lower solubility in fasted state simulated intestinal fluids (FaSSIF). However, compounds with delayed absorption had higher solubility in FaSSIF. The study noted that an AUC increase in the fed state did not occur with compounds that has low lipid solubility (logP <1.59).

Role of Dietary Factors

FOOD COMPOSITION: Foods rich in fats can significantly impact the absorption of certain medications. Fat-soluble drugs, such as some vitamins and lipid-lowering medications, are absorbed more readily in the presence of dietary fats. Also, dietary fibre, found abundantly in fruits, vegetables, and whole grains, can bind to drugs, and delay their absorption. Other drugs bind to proteins in the bloodstream, and the presence of dietary proteins can compete for these binding sites. This competition can alter the concentration of the free drug available for absorption, affecting its bioavailability.

MEAL TIMING: The timing of meals in relation to medication intake is crucial. Some drugs are best absorbed on an empty stomach earlier in the day as a result of overnight fasting, as food can interfere with their absorption. Conversely, other medications should be taken with meals to enhance their absorption and reduce the risk of GI irritation.

GASTROINTESTINAL PH: The acidity of the stomach plays a pivotal role in drug absorption. Some medications, such as acid-sensitive drugs like certain antibiotics, can be rendered less effective in the presence of acidic food, thus decreasing the drug’s potential therapeutic effect.

FORMULATION: The formulation (tablet, capsule of liquid) of a drug can also influence its absorption in the presence of food or dietary factors. For example, some drugs are formulated as enteric-coated tablets to prevent degradation in the acidic environment of the stomach, allowing better absorption and efficacy.

Implications for Dosing Strategies

INDIVIDUALIZED DOSING: Recognizing the impact of diet on drug absorption underscores the importance of individualized dosing regimens. Factors such as the test systems’ typical diet, meal timing preferences, and nutritional status should all be considered when assessing food effects. Hence in a nonclinical study, the test diet regimens are controlled with timed feeding and a certified dietary composition.

TIMING RECOMMENDATIONS: Attentive Science data provide detailed information to inform the optimal time to take medications in relation to meals to enhance efficacy and reduce the risk of adverse effects. As a result of Attentive Science nonclinical data sets, clinical trial participants might be advised to take a lipid-lowering medication with their largest meal of the day to maximize absorption.

MONITORING AND ADJUSTING: Regular monitoring of responses to medications, coupled with adjustments in dosing based on dietary factors, can improve treatment outcomes. Attentive Science data assist in guiding dosing schedules or considering alternative formulations based on dietary habits of the intended clinical population.

In closing…

Attentive Science stands at the forefront of unravelling these complexities, dedicated to pioneering research and innovation in drug delivery and pharmacokinetics. As we navigate the pharmacokinetic maze, we envisage a world where every dose is optimized for maximal therapeutic benefit.

Connect with us at Attentive Science as our team of Scientists help you unravel the complexities of dietary factors on drug absorption, bioavailability, and the pivotal role they play in shaping therapeutic outcomes.

References:

• Smith, S. D., & Park, K. (2015). The Effect of Food on Drug Bioavailability. Biopharmaceutics & Drug Disposition, 36(2), 75–85. https://doi.org/10.1002/bdd.1914
• Wen, H., & Jung, H. (2017). Pharmacokinetics and Pharmacodynamics: The Dynamics of the Body and Drugs. Elsevier.
• Dresser, G. K., & Bailey, D. G. (2010). The Effects of Fruit Juices on Drug Disposition: A New Model for Drug Interactions. European Journal of Clinical Investigation, 40(9), 757–763. https://doi.org/10.1111/j.1365-2362.2010.02364.x
• Omachi, F., Kaneko, M., Iijima, R., Watanabe, M., & Itagaki, F. (2019). Relationship between the effects of food on the pharmacokinetics of oral antineoplastic drugs and their physicochemical properties. Journal of Pharmaceutical Health Care and Sciences, 5(1). https://doi.org/10.1186/s40780-019-0155-1