Sites of Drug Biotransformation

Glucuronide conjugate at either COOH or phenotic OH group 

Some drugs (c.g.. lidocaine) arc removed so effectively b) ftrst-pass metabolism that they are ineffective when given orally. Nitroglycerin is administered buccally to bypass the liver. 

Although other tissues, such as kidney, lungs, adrenal glands, placenta, brain, and skin, have some drug-mctaboliz-ing capability, the biotransfurmutiuns that they carry out often are mure substrate selective and more limited to particular types of reaction (e.g., oxidation, glucuronidation). In many in.stanccs. the full metabolic capabilities of these tis-Mies have not been explored fully. 

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Biotransformation and Biliary Excretion. The liver is a major site of drug metabolism, but it is also an important excretory organ. Some of the... 

Drugs are eliminated from the body by metabolism and excretion. The liver is the major site of drug metabolism however, other tissues also contain drug-metabolizing enzymes and, therefore, contribute to the biotransformation of selected drugs. The kidneys are involved in the elimination of many drugs and virtually all drug metabolites. 

Metabolic stability in human liver preparations may represent a suitable experimental tool to obtain relevant pharmacokinetic information in an early phase of drug discovery. Compounds which are metabolized principally by the liver can be identified and studied in more detail to determine the principal sites of biotransformation. 

Pharmacokinetics is specifically concerned with the transfer of a drug through the body by the processes of absorption, distribution, biotransformation, and excretion. A drug s dosage and pharmacokinetic properties will determine the concentrations that will be reached, and therefore the intensity of effect produced. Ultimately, these processes determine the bioavailabiUty of a drug, or the degree to which it reaches the intended site of action. 

When levels of the drug decline in plasma, usually due to biotransformation and excretion, the drug then redistributes away from its site of action into other tissues (e.g., drugs may distribute across the placenta during pregnancy). This is a passive process, but lipid-soluble drugs penetrate the most. 

As mentioned above, bioavailability is the degree to which a drug reaches the intended site of action. The amount of drug that reaches systemic circulation will depend on the processes of absorption, distribution, and biotransformation (when the route of administration exposes the drug to first-pass metabolism). Pharmacokinetics are often linear and when they are nonlinear it is often due to a saturation of protein binding, metabolism, or active renal transport. 

Pharmacokinetics What the body does to the drug. The process of drug absorption from the site of administration, distribution to the target organ and other bodily compartments, metabolism or biotransformation (if necessary), and eventual elimination. 

Pharmacokinetics is defined as the study of the quantitative relationship between administered doses of a drug and the observed plasma/blood or tissue concentrations. The field of pharmacokinetics is concerned with drug absorption, distribution, biotransformation, and excretion or elimination. These processes, in addition to the dose, determine the concentration of drug at the effector or active site and, therefore, the intensity and duration of drug effect. 

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