ABSTRACT
Introduction ............................................................................................................ 108 Factors That Affect Drug Pharmacokinetics .......................................................... 109
Gastric Emptying and Intestinal Transit Time .................................................. 109 Presystemic Clearance ...................................................................................... 109 Hepatic Metabolism .......................................................................................... 110
Basic Principles of Nutrient-Drug Interactions ..................................................... 112 Relation of Meal Timing and Drug Absorption ..................................................... 112 Drug and Nutrient Transport Systems.................................................................... 113 Interactions between Enteral Feedings and Medications Revisited ....................... 114 Effect of Malnutrition on Pharmacokinetic Parameters ......................................... 115 Impact of Nutritional Status on Pharmacokinetic Properties ................................. 117
Absorption ......................................................................................................... 117 Distribution ....................................................................................................... 117 Metabolism ........................................................................................................ 118 Clearance ........................................................................................................... 118 Impact of Kwashiorkor on Pharmacokinetics ................................................... 119 Drug Therapy in Marasmus............................................................................... 119 Obesity .............................................................................................................. 120
Inuence of Dietary Manipulation on Pharmacokinetics ...................................... 121 Inuence of Specic Nutrients on Pharmacokinetics ............................................ 134
Carbohydrates ................................................................................................... 134 Protein ............................................................................................................... 134 Dietary Fat ......................................................................................................... 135 Minerals............................................................................................................. 136 Vegetables ......................................................................................................... 136 Drug and Grapefruit Juice Interactions ............................................................. 136 Other Dietary Restrictions................................................................................. 137 Effect of Beverage Type on Drug Bioavailability ............................................. 137 Parenteral Nutrition ........................................................................................... 138
The nutritional status of a patient and the constituents of their diet can signicantly affect the pharmacodynamic (e.g., afnities to receptors or tissues) and pharmacokinetic (i.e., absorption, distribution, metabolism, transport, and elimination) properties of drugs.1 Gastrointestinal motility, blood ow, gastric secretions, and enzymatic activity, which affect biotransformation and disposition of drugs, can all be inuenced by a variety of nutritional components (Figure 6.1). The extent of these effects, however, is extremely variable and patient specic, confounded by many other factors, and oftentimes unpredictable. Periods of increased caloric demand (i.e., during
Inuence of Medications on Nutrient Status ......................................................... 138 Nutrient Transport ............................................................................................. 138 Nutrient Absorption ........................................................................................... 138 Nutrient Metabolism ......................................................................................... 138 Medication-Associated Fluid and Electrolyte Disturbances ............................. 139 Glucose .............................................................................................................. 140 Fat ...................................................................................................................... 140
Gastrointestinal Complications .............................................................................. 142 Alterations in Appetite ...................................................................................... 142
Examples of Drug-Nutrient Interactions in Specic Infectious Disease Processes ................................................................................................... 144
Tuberculosis ...................................................................................................... 144 Human Immunodeciency Virus ....................................................................... 144
Conclusion ............................................................................................................. 145 References .............................................................................................................. 145
FIGURE 6.1 Relation between nutritional factors and drug therapy.
