Terms Integral to this discussion is a review of the basic terminology utilized in clinical pharmacology The following terms are described in greater detail in referenced texts.5,6 Absorption is the process of drug movement from the site of administration or application into systemic circulation The rate (e.g., time to maximal concentration; tmax) and extent (e.g., bioavailability) of absorption can be impacted by drug factors (e.g., formulation, solubility, protein binding, lipid/water-partition coefficient) and/or patient factors (e.g., protein binding capacity, gastric emptying time, portal venous stasis) Area under the curve (AUC) is the area under the plasma drug concentration–time curve In the domain of pharmacokinetics, AUC and maximal plasma drug concentration (Cmax) represent the important parameters by which one can quantitate how much systemic exposure (e.g., dose-exposure relationship) occurs over a given period of time (Fig 79.1) Time to maximal plasma drug concentration (Tmax) represents the time required for drug absorption after extravascular administration Plasma concentration vs time curve This example of a pharmacokinetic profile was acquired over 12 hours Each black dot represents the time point at which a plasma sample was obtained The area under the plasma concentration curve (AUC) FIG 79.1 is the amount of drug exposure that occurs over a given time period This example demonstrates the drug exposure over 12 hours, although this value can be extrapolated to infinity The maximal plasma drug concentration (Cmax) and time to maximal plasma drug concentration (Tmax) are demonstrated here Bioavailability is the fraction of a drug, administered by a route other than intravenous, that reaches the systemic circulation The aforementioned drug and patient factors influence the degree of systemic exposure that occurs after a given dose (e.g., dose-exposure relationship) Clearance is the pharmacokinetic measurement of the volume of plasma from which a substance is completely removed per unit time Disposition refers to the entire process of absorption, distribution, metabolism, and elimination (ADME) that influences the pharmacokinetics of a drug Distribution is a pharmacokinetic term that describes the reversible transfer of a drug from one location to another within the body Metabolism is the biotransformation process by phase 1 and/or 2 metabolizing enzymes to enhance the excretion of drugs Of note, metabolism may contribute to the inactivation (e.g., verapamil) or activation (e.g., enalaprilat) of a drug moiety Phase 1 is composed of oxidation, reduction, hydrolysis, and methylation reactions that collectively serve to increase the polarity of a drug Phase 1 metabolism is performed primarily by a group of oxidases referred to as cytochrome p450 enzymes (CYPs) Conversely, phase 2 metabolism is responsible for converting drugs into a more water-soluble form for excretion Several major gene families that are involved in phase II reactions have been identified, including N-acetyltransferases (NAT), uridine diphosphate–glucuronosyl transferases (UGT), glutathione S-transferases (GST), and sulfotransferases (SULT) Analogous to the CYP450 families, these gene families also have individual isoforms, each with its own ontogenic profile Pharmacodynamics entails both the qualitative and quantitative description of drug effect Simply put, this is what a drug and/or metabolite does to the body Pharmacokinetics describes the change of drug concentration in the drug product and changes in concentration of a drug and/or its metabolite in the human body following administration This term represents the dose- exposure relationship of drug administration Simply put, this is what the body does to a drug and/or metabolite Pharmacogenetics describes interindividual variation in DNA sequence related to drug absorption and distribution (PK) or drug action (PD) Pharmacogenomics is the application of genomic principles and technologies in drug discovery to pharmacologic function, disposition, and therapeutic response