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19DRUG ABSORPTION, DISTRIBUTION AND ELIMINATION; PHARMACOKINETICS I. DRUG ADMINISTRATION Often the goal is to attain a therapeutic drug concentration in plasma from which drug enters the tissue (therapeutic window between toxic concentration and minimal effective concentration). A. Enteral Routes 1. Sublingual (buccal) Certain drugs are best given beneath the tongue or retained in the cheek pouch and are absorbed from these re gions into the local circulation. These vascular areas are ideal for lipid-soluble drugs that would be metabolized in the gut or liver, sin ce the blood vessels in the mouth bypass the liver (do not undergo first pass liv er metabolism), and drain directly into the systemic circulation. This r oute is usually reserved for nitrates and certain hormones. 2. Oral By far the most common route. The passage of drug from the gut into the blood is influenced by biologic and phys icochemical factors (discussed in detail below), and by the dosage form. For most drugs, two- to five-fold differences in the rate or extent of gastrointestinal ab sorption can occur, depending on the dosage form. These two characteristics, rate and completeness of absorption, comprise bioavailability . Generally, the bioavailability of oral drugs follows the order: solution > suspension > capsule > tablet > coated tablet. 3. Rectal The administration of suppositories is usually reserved for situations in which oral administration is difficult. This route is more frequently used in small children. The rectum is devoid of villi, thus absorption is often slow. B. Parenteral Routes 1. Intravenous injection Used when a rapid clinical response is necessary, e.g., an acute asthmatic episode. This route allows one to achieve relatively precise drug concentrations in the plasma, since bi oavailability is not a concern. Most drugs should be injected over 1-2 minutes in order to prevent the occurrence of very high drug concentra tions in the injected vein, possibly causing adverse effects. Some drugs , particularly those with narrow therapeutic indices or short half-lives, are best administered as a slow IV infusion or drip. 2. Intra-arterial injection Used in certain special situations, notably with anticancer drugs, in an effort to deliver a high concentrati on of drug to a particular tissue. Typically, the injected artery lead s directly to the target organ.
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