Food products, herbal medicines, dietary supplements, pharmaceutical excipients, co-administered drugs, and other chemicals can alter drug pharmacokinetics and consequently the therapeutic efficiency of a drug treatment. Their effect can be chemical (e.g., accelerated drug degradation in the gastrointestinal [GI] tract) or physical (e.g., enhanced or decreased aqueous solubility), or they can affect enzyme activity and active transport through inhibition or activation. Pharmacokinetic studies can give important information on how various xenobiotics affect the therapeutic efficacy of drugs. Such studies can give pharmaceutical formulators important information on excipient selection, that is, which one to use and which one to avoid. Furthermore, pharmacokinetic studies can tell patients which food products and herbal medicines they can safely consume during a given drug treatment and which they should avoid and also give information about drug–drug interactions. A few examples are discussed below.

Food, especially fatty food, is known to enhance the oral bioavailability of some poorly water-soluble, lipophilic drugs such as carbamazepine and griseofulvin by increasing their dissolution rate in the GI tract. Food may enhance the oral bioavailability of drugs by reducing their fist-pass metabolism (e.g., propafenone [Figure 6.1], metoprolol, and propranolol) or by delaying gastric emptying (e.g., phenytoin and spironolactone). Food can also delay drug absorption from the GI tract. For example, high-fiber foods are known to reduce the oral bioavailability of digoxin through the formation of digoxin–fiber complexes. Digoxin tablets are best taken on an empty stomach, especially if the patient is on a high-fiber diet. Tetracycline antibiotics form hydrophilic complexes (chelates) with various metal ions such as iron (Fe²⁺), zinc (Zn²⁺), magnesium (Mg²⁺), and calcium (Ca²⁺). These metal complexes, which consist of one metal ion and two tetracycline molecules, increase the apparent molecular weight of the parent drug, tetracycline, from 444 daltons (Da) to well over 900 Da, as well as the number of hydrogen bond acceptors and donors. Consequently, the bioavailability of tetracycline is significantly reduced upon formation of metal complexes (Figure 6.2). Dairy products, antacids, and iron supplements should not be consumed during tetracycline treatment. Cyclodextrins are enabling pharmaceutical excipients that enhance aqueous solubility of many lipophilic drugs [3]. Glibenclamide is a hypoglycemic agent that is practically insoluble in water, and consequently, drug dissolution in the GI tract is the rate-limiting step in its absorption (i.e., that glibenclamide is a Biopharmaceutics Classification System [BCS] Class II drug). In a canine study, the absolute bioavailability (F) of the pure drug (i.e.,

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