food interaction

• Food-drug interactions


  Alterations of pharmacokinetics or pharmacodynamics of a drug or nutritional element or a compromise in nutritional status as a result of the addition of a drug, resulted from physical, chemical, physiological or pathophysiological relationship of the interactions
• What the body does to the drugs? (ADME)
• What the drug does to the body? (TE, AE)
• Food-drug interactions


  • Have profound influence on the effectiveness of the drug therapy & the AEs profiles of drugs
  • Decreased bioavailability of a drug - predisposes to treatment failure
  • Increased bioavailability - increases the risk of AEs & precipitate toxicities
  • Also increase the therapeutic value of the drugs by improving the drug absorption or reducing its side effects
  • The magnitude of change determines whether the interaction is clinically significant & requires intervention

  
• Type of drug interactions

  • Drug - drug (prescription drugs or OTC)
  • Drug – herbal products (supplements)
  • Drug – nutrients (enteral or parenteral)

  
• Drugs – nutrients interactions

  • Ex vivo deactivations of drugs (Type I)
  • Affects absorption (Type II)
  • Affect systemic or physiologic disposition (Type III)
  • Affects elimination or clearance (Type IV)

  
• Ex vivo bio-deactivation


  Active ingredients are deactivated before being absorbed
• Biopharmaceutical inactivation


  Biochemical or physical reactions, interactions between drug & nutritional or formulation
• Biopharmaceutical deactivations


  • Take place when the interacting agents are in direct physical contact before the nutrients or drugs enter the body
  • Usually occur in the delivery device (enteral or parenteral feeding infusion tubing, infusion bags) or during the compounding process itself (mixing, combining, altering)
  • Examples: hydrolysis, oxidation, neutralisation, precipitation, complexation
• Hydrolysis


  Hydrolysis the cleavage of chemical bonds by the addition of water (H-OH)
• Hydrolytic process involving the direct mixing of enteral feeding formula & vehicles used in oral liquid medications (eg: syrup)
• Biochemical or physical reactions


  • Biophysical changes as the result of the interaction
  • Eg: physical incompatibility between IV administered drugs & parenteral nutrition
  • Compatibility of IV administered products - cannot rely on visual inspection, use published references
  • Compatibility of parenteral nutrition is important – refer to publication or pharmacist

  
• Parenteral products (nutrient interactions)


  • Formation of non-dissolvable or unstable intermediates (crystals, precipitates in the solution)
  • Systemic exposure to these by-products can result in life threatening events, eg: occlusion of blood vessels
  • Visual detection is possible for precipitation from Ca & P (formation of in soluble particles)
  • But some precipitants may be too small to be visible by naked eyes

  
• Parenteral lipid products (formulation)

  • Formulated as opaque emulsions (oil mixed in water)
  • Physical incompatibility cannot be determined by visual inspection
  • Addition of a drug into the infusion device containing IV lipid emulsion resulting in the disruption of the emulsion formulation
  • Eg: adding large amount of heparin into total nutrient admixture

  
• Minimising type I interactions

  1. Parenteral products: Do not mix drugs directly with parenteral formulas, Use Y site

  2. Enteral feeding: Flush tubing with water before & after drug administration, Use preformulated oral solutions, elixirs, or suspensions instead of crushing tablets when administering drugs through enteral feeding tubes, to increase dose accuracy & minimize clogging

  
• Type II – absorption


  Interactions affecting absorption phase, Affect drugs & nutrients delivered only by mouth or via enteral delivery devices, Cause either an increase or decrease of oral bioavailability of the drug or nutrient

  
• Type II interactions


  • Pre systemic metabolism (type A interaction)
  • Pre systemic transport (type B interaction)
  • Pre systemic binding / complexation (type C interaction)
• Type A interaction (pre-systemic metabolism)

  Involves the inhibition or induction of the enzymes present in the GI or liver (CYP3A4)
• Type A interaction


  • Grapefruit juice - enhancement of oral absorption of many drugs that are substrates to CYP3A4 enzymes (carbamazepine, cyclosporine, felodipine, triazolam)
  • Orlistat & fat-soluble vitamins: orlistat decreases the absorption of dietary fat via inhibition of lipase in GIT. The unabsorbed fat act as vehicle to trap fat-soluble vitamin in the intestinal lumen & reduces the bioavailability of these vitamins

  
• Meals vs drug absorption

  Drugs given IV are not expected to be influenced by food, But for orally-administered drugs, delay in absorption may occur, Low bioavailability – may be due to susceptible to food interactions, Decreased bioavailability → therapeutic failure, High bioavailability (>90%) – effect of food may not be significant, Increased bioavailability → risk of toxicities, Meal intake stimulates gastric secretion: some drugs are not acid-stable (exposure to acid leads to chemical degradation), others are dependent on acidity for good absorption

  
• High-fat content stimulates release of BS

  Increased absorption of lipophilic drugs, Eg: anti-retroviral drug (saquinavir), High-fat content also releases high [CCK]: slows GI motility, increases contact time increases absorption

  
• Drugs to be taken with food

  • Cefuroxime, Erythromycin (antibiotics), Lovastatin, Lithium (To maximise drug absorption)
  • Non-steroidal anti-inflammatory drugs, Prednisolone, Valproate, Metformin (To avoid stomach irritation)
  • Anti-diabetics (To avoid the risk of hypoglycemia)
• Drugs not to be taken with food

  • Antibiotics: ampicillin, ciprofloxacin, doxycycline, tetracycline, Anti-HYP: captopril (Taken at least 1H before OR 2H after a meal, To maximise drug absorption, To avoid physical interaction that can interfere with absorption process e.g. complexation)
• Type B interaction (pre-systemic transport)

  The agents may alter the function of transporters (intestinal P-glycoprotein), the transit time, or the dissolution of the object compound, The mechanism may involve functional alteration (inhibition) or physiologic alteration (pH) causes a reduction in bioavailability of the object agent
• Type B interaction


  • Cyclosporine & water soluble vitamin E may interact via this mechanism
• Type c interaction (pre-systemic binding / complexation)

  In some cases complexation, binding or other deactivating processes occur in the GIT, impairing the object agent from being absorbed, The agents are bound or complexed together resulting in a reduction in oral bioavailability, This interaction differs from ex vivo biopharmaceutical inactivation in that it takes place inside GIT, rather than in the delivery device, Specific enzymes or transporters may not be involved
• Type C interaction


  • Coadministration of tetracycline or ciprofloxacin + dairy products
• SYSTEMIC / PHYSIOLOGIC INTERACTIONS


  Affect systemic or physiologic dispositions, Occur after the drug or the nutritional element has been absorbed from the GIT & entered in to the systemic circulation, Mechanisms: changing the cellular or tissue distribution, systemic metabolism or transport, or penetration to specific organ/tissues of the drugs or nutrients, changing the function of other co-factors (eg: clotting factors) or hormones
• Tissue distribution


  Protein binding: most drugs are loosely bound to plasma proteins, displacement from binding sites will increase the 'free' or 'unbound' drugs, effect is significant with highly-bound drugs, Corticosteroid alter Ca & Vit. D disposition by affecting osteocalcin & probably PTH hormone activities – increased risk of osteoporosis, Antiepileptic drug, valproic acid, can deplete carnitine causes hyperammonemia & hepatic encephalopathy without other evidence of hepatic injury - fatality has been reported
• Interaction affecting clearance


  Affect the elimination or clearance of drugs or nutrients, modulation, antagonism, or impairment of renal or entero-hepatic elimination, Inhibition of enzyme activities, increase bioavailability of drugs i.e. toxicities, Interfere with metabolism, Na-rich food - Li exchanges w Na, increase Na excretion, Low Na diet – potential for Li toxicity, K-rich food – increase potential of K toxicity with sparing diuretics, ARBs, ACE inhibitors, calcineurin inhibitors

  
• Reduced metabolism & clearance of drugs

  • Grape fruit juice enzyme inhibitor, Inhibits the metabolism of warfarin, diazepam, midazolam, nifedipine, verapamil, erythromycin

  
• 5 common harmful food-drug interactions

  • Ca-rich food + antibiotics
  • Pickled, cured, fermented foods + MAOIs
  • Vitamin K-rich foods + warfarin
  • Alcohol + prescription stimulants
  • Grapefruit and grapefruit juice + statins