Drug-nutrient interactions.

Drug-nutrient interactions are defined as physical, chemical, physiologic, or pathophysiologic relationships between a drug and a nutrient. The causes of most clinically significant drug-nutrient interactions are usually multifactorial. Failure to identify and properly manage drug-nutrient interactions can lead to very serious consequences and have a negative impact on patient outcomes. Nevertheless, with thorough review and assessment of the patient's history and treatment regimens and a carefully executed management strategy, adverse events associated with drug-nutrient interactions can be prevented. Based on the physiologic sequence of events after a drug or a nutrient has entered the body and the mechanism of interactions, drug-nutrient interactions can be categorized into 4 main types. Each type of interaction can be managed using similar strategies. The existing data that guide the clinical management of most drug-nutrient interactions are mostly anecdotal experience, uncontrolled observations, and opinions, whereas the science in understanding the mechanism of drug-nutrient interactions remains limited. The challenge for researchers and clinicians is to increase both basic and higher level clinical research in this field to bridge the gap between the science and practice. The research should aim to establish a better understanding of the function, regulation, and substrate specificity of the nutrient-related enzymes and transport proteins present in the gastrointestinal tract, as well as assess how the incidence and management of drug-nutrient interactions can be affected by sex, ethnicity, environmental factors, and genetic polymorphisms. This knowledge can help us develop a true personalized medicine approach in the prevention and management of drug-nutrient interactions.

[1]  Andreas Rolfs,et al.  The ABCs of solute carriers: physiological, pathological and therapeutic implications of human membrane transport proteins , 2004, Pflügers Archiv.

[2]  M. Frye,et al.  Valproate-induced hyperammonemic encephalopathy: an update on risk factors, clinical correlates and management. , 2012, General hospital psychiatry.

[3]  Y. Sai,et al.  Biochemical and molecular pharmacological aspects of transporters as determinants of drug disposition. , 2005, Drug metabolism and pharmacokinetics.

[4]  B. Hirschowitz,et al.  Vitamin B12 deficiency in hypersecretors during long‐term acid suppression with proton pump inhibitors , 2008, Alimentary pharmacology & therapeutics.

[5]  G. Coppola,et al.  Plasma free carnitine in epilepsy children, adolescents and young adults treated with old and new antiepileptic drugs with or without ketogenic diet , 2006, Brain and Development.

[6]  F. Moreno,et al.  Carnitine levels in valproic acid-treated psychiatric patients: a cross-sectional study. , 2005, The Journal of clinical psychiatry.

[7]  D. Stafford.  The vitamin K cycle , 2005, Journal of thrombosis and haemostasis : JTH.

[8]  R. Dickerson,et al.  Clinical relevancy of the levothyroxine-continuous enteral nutrition interaction. , 2010, Nutrition in clinical practice : official publication of the American Society for Parenteral and Enteral Nutrition.

[9]  I. Tamai,et al.  Effect of milk on the pharmacokinetics of oseltamivir in healthy volunteers. , 2011, Journal of pharmaceutical sciences.

[10]  M. Imamura,et al.  Expression profiles of various transporters for oligopeptides, amino acids and organic ions along the human digestive tract. , 2005, Biochemical pharmacology.

[11]  G. Boudry,et al.  Role of intestinal transporters in neonatal nutrition: carbohydrates, proteins, lipids, minerals, and vitamins. , 2010, Journal of pediatric gastroenterology and nutrition.

[12]  S. Solomon,et al.  Vitamin B12 Deficiency Associated With Concomitant Metformin and Proton Pump Inhibitor Use , 2012, Diabetes Care.

[13]  R. Jensen,et al.  Association of Long-Term Proton Pump Inhibitor Therapy with Bone Fractures and Effects on Absorption of Calcium, Vitamin B12, Iron, and Magnesium , 2010, Current gastroenterology reports.

[14]  D. Thwaites,et al.  Hijacking solute carriers for proton-coupled drug transport. , 2010, Physiology.

[15]  G. Triadafilopoulos,et al.  Adverse Effects of Long-Term Proton Pump Inhibitor Therapy , 2011, Digestive Diseases and Sciences.

[16]  J. Rotschafer,et al.  Decreased in vitro fluoroquinolone concentrations after admixture with an enteral feeding formulation. , 2000, JPEN. Journal of parenteral and enteral nutrition.

[17]  C. de la Piedra,et al.  Bone Disease Induced by Phenytoin Therapy: Clinical and Experimental Study , 2009, European Neurology.

[18]  N. Rapin,et al.  Intestinal transporters for endogenic and pharmaceutical organic anions: the challenges of deriving in‐vitro kinetic parameters for the prediction of clinically relevant drug–drug interactions , 2012, The Journal of pharmacy and pharmacology.

[19]  O. Witte,et al.  Long-term anticonvulsant therapy leads to low bone mineral density--evidence for direct drug effects of phenytoin and carbamazepine on human osteoblast-like cells. , 2012, Experimental and clinical endocrinology & diabetes : official journal, German Society of Endocrinology [and] German Diabetes Association.

[20]  D. Stafford,et al.  The conversion of vitamin K epoxide to vitamin K quinone and vitamin K quinone to vitamin K hydroquinone uses the same active site cysteines. , 2007, Biochemistry.

[21]  B. Hagenbuch,et al.  OATPs, OATs and OCTs: the organic anion and cation transporters of the SLCO and SLC22A gene superfamilies , 2012, British journal of pharmacology.

[22]  M. Bair,et al.  Young woman presenting with small bowel obstruction. , 2012, Gastroenterology.

[23]  F. Kamali,et al.  Vitamin K epoxide reductase complex subunit 1 (VKORC1 ) polymorphism influences the anticoagulation response subsequent to vitamin K intake: a pilot study , 2008, Journal of thrombosis and haemostasis : JTH.

[24]  Bruno Hagenbuch,et al.  The expression and function of organic anion transporting polypeptides in normal tissues and in cancer. , 2012, Annual review of pharmacology and toxicology.

[25]  K. Inui,et al.  Inhibitory effect of zinc on the absorption of beta-lactam antibiotic ceftibuten via the peptide transporters in rats. , 2008, Drug metabolism and pharmacokinetics.

[26]  K. McColl.  Effect of Proton Pump Inhibitors on Vitamins and Iron , 2009, The American Journal of Gastroenterology.

[27]  H. Saito,et al.  Inhibitory Effect of Zinc on PEPT1-Mediated Transport of Glycylsarcosine and β-Lactam Antibiotics in Human Intestinal Cell Line Caco-2 , 2003, Pharmaceutical Research.

[28]  L. Bauer.  Interference of oral phenytoin absorption by continuous nasogastric feedings , 1982, Neurology.

[29]  S. R. Abel,et al.  Effect of enteral feeding with ensure on oral bioavailabilities of ofloxacin and ciprofloxacin , 1994, Antimicrobial Agents and Chemotherapy.

[30]  S. Cohn,et al.  Enteric absorption of ciprofloxacin during tube feeding in the critically ill. , 1996, The Journal of antimicrobial chemotherapy.

[31]  Leslie Z Benet,et al.  Intestinal drug transporters: an overview. , 2013, Advanced drug delivery reviews.

[32]  R. Dickerson.  Warfarin resistance and enteral tube feeding: a vitamin K-independent interaction. , 2008, Nutrition.

[33]  C. Colón-Emeric,et al.  A review of the effect of anticonvulsant medications on bone mineral density and fracture risk. , 2010, The American journal of geriatric pharmacotherapy.

[34]  R. Dickerson,et al.  Vitamin K‐Independent Warfarin Resistance After Concurrent Administration of Warfarin and Continuous Enteral Nutrition , 2008, Pharmacotherapy.

[35]  O. Mimoz,et al.  Pharmacokinetics and absolute bioavailability of ciprofloxacin administered through a nasogastric tube with continuous enteral feeding to critically ill patients. , 1998, Intensive care medicine.

[36]  M. H. Ensom,et al.  Phenytoin and Enteral Feedings: Does Evidence Support an Interaction? , 2000, The Annals of pharmacotherapy.

[37]  B. Menon,et al.  The effect of anti epileptic drug therapy on serum 25-hydroxyvitamin D and parameters of calcium and bone metabolism—A longitudinal study , 2010, Seizure.

[38]  D. Thwaites,et al.  The SLC36 family of proton‐coupled amino acid transporters and their potential role in drug transport , 2011, British journal of pharmacology.

[39]  Mridula Nair,et al.  Clinical consequences of polypharmacy in elderly: expect the unexpected, think the unthinkable , 2007, Expert opinion on drug safety.

[40]  M. Mikati,et al.  Predictors of bone density in ambulatory patients on antiepileptic drugs. , 2008, Bone.

[41]  B. Tepeš,et al.  Long-Term Acid Inhibition: Benefits and Harms , 2011, Digestive Diseases.

[42]  M. Grover,et al.  Association Between Proton Pump Inhibitor Use and Anemia: A Retrospective Cohort Study , 2011, Digestive Diseases and Sciences.

[43]  R. Valuck,et al.  A case-control study on adverse effects: H2 blocker or proton pump inhibitor use and risk of vitamin B12 deficiency in older adults. , 2004, Journal of clinical epidemiology.

[44]  D. Thwaites,et al.  H+‐coupled nutrient, micronutrient and drug transporters in the mammalian small intestine , 2007, Experimental physiology.

[45]  A Pavani,et al.  Optimization of warfarin dose by population-specific pharmacogenomic algorithm , 2011, The Pharmacogenomics Journal.

[46]  Leslie Z. Benet,et al.  The Role of Transporters in the Pharmacokinetics of Orally Administered Drugs , 2009, Pharmaceutical Research.

[47]  F. Chiarelli,et al.  Valproate-Induced Hyperammonemic Encephalopathy , 2002, Metabolic Brain Disease.