Food-Drug Interactions

Food-drug interactions are changes in the absorption, and therefore the bioavailability, of a drug caused by the presence of food or specific dietary constituents in the gastrointestinal tract. Food can delay, reduce, or increase the amount of drug reaching the systemic circulation through effects on gastric emptying, dissolution, complexation, and the metabolising and transport systems of the gut wall.

Definition

A food-drug interaction is a food- or diet-induced alteration in the rate or extent of drug absorption, mediated by physiological and biochemical changes in the gastrointestinal tract that modify the drug's bioavailability.

Scope

The entry covers the principal ways food alters drug absorption, the distinction between effects on rate and extent of bioavailability, illustrative interactions such as the grapefruit-juice effect on intestinal metabolism, and why fed-versus-fasted conditions are standardised in bioavailability studies. It treats food-drug interactions as a reference topic in biopharmaceutics, not as individualised dietary or dosing advice.

Core questions

• How can food change the amount and speed of drug absorption?
• Which physiological and biochemical mechanisms underlie these changes?
• Why can a specific food such as grapefruit juice raise systemic exposure to certain drugs?
• Why are bioavailability studies conducted under defined fed and fasted conditions?

Key concepts

• Effects on rate versus extent of absorption
• Gastric emptying and transit time
• Dissolution and solubility changes
• Complexation and chelation
• Inhibition of intestinal metabolism and transporters
• Fed-versus-fasted study conditions

Mechanisms

Food influences drug absorption through several routes. It slows gastric emptying, which can delay the time to peak concentration; it changes gastrointestinal pH, bile secretion, and splanchnic blood flow, which can raise or lower the extent absorbed; and dietary constituents can bind drug in the lumen, as when polyvalent cations chelate certain agents and reduce their uptake. Some foods act biochemically rather than physically: grapefruit juice contains furanocoumarins that inhibit intestinal drug-metabolising enzymes, reducing presystemic metabolism and thereby increasing the bioavailability of susceptible drugs, an effect demonstrated for felodipine by Bailey and colleagues. Because these effects can be substantial, regulatory bioavailability and bioequivalence studies specify standardised fed and fasted conditions so that food effects are characterised rather than confounding.

Clinical relevance

Food-drug interactions explain why instructions about taking a medicine with or without food exist and why certain dietary items are flagged for particular drugs. They are a reference concept for understanding how diet modifies exposure; they describe a pharmacological phenomenon and are not a substitute for individualised dietary or medication advice from a qualified professional.

Evidence & guidelines

The mechanisms by which food alters absorption were synthesised in Welling's review, which remains a standard reference. The grapefruit-juice interaction, characterised by Bailey and colleagues for felodipine and extended to older adults by Dresser and colleagues, became the canonical example of a food acting through inhibition of intestinal metabolism, and such food effects are formally evaluated under defined fed and fasted conditions in bioavailability assessment.

History

Recognition that meals could change drug absorption grew with quantitative bioavailability studies in the second half of the twentieth century, summarised in reviews such as Welling's. The 1989 chance observation, reported in detail by Bailey and colleagues in 1993, that grapefruit juice markedly raised felodipine exposure revealed a distinct biochemical class of food-drug interaction acting on intestinal metabolism, and follow-up work extended its relevance to vulnerable populations.

Key figures

• Peter Welling
• David Bailey
• George Dresser

Seminal works

• welling-1996
• bailey-1993

Frequently asked questions

Can food increase as well as decrease drug absorption?

Yes. Depending on the drug and mechanism, food can reduce absorption (for example by binding the drug), delay it (by slowing gastric emptying), or increase it (for example by enhancing dissolution or, as with grapefruit juice, inhibiting presystemic metabolism).

Why does grapefruit juice affect certain drugs?

Grapefruit juice contains furanocoumarins that inhibit drug-metabolising enzymes in the intestinal wall, reducing first-pass metabolism of susceptible drugs and thereby increasing the amount that reaches the systemic circulation.