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Chapter 3: Pharmacokinetics

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INTRODUCTION

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Pharmacokinetics denotes the effects of biologic systems on drugs. The major processes involved in pharmacokinetics are absorption, distribution, and elimination. Appropriate application of pharmacokinetic data and a few simple formulas makes it possible to calculate loading and maintenance doses.

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High-Yield Terms to Learn
Volume of distribution (apparent) The ratio of the amount of drug in the body to the drug concentration in the plasma or blood. Units: liters
Clearance The ratio of the rate of elimination of a drug to the concentration of the drug in the plasma or blood. Units: volume/time, eg, mL/min or L/h
Half-life The time required for the amount of drug in the body or blood to fall by 50%. For drugs eliminated by first-order kinetics, this number is a constant regardless of the concentration. Units: time
Bioavailability The fraction (or percentage) of the administered dose of drug that reaches the systemic circulation
Area under the curve (AUC) The graphic area under a plot of drug concentration versus time after a single dose or during a single dosing interval. Units: concentration × time; eg, mg min/mL
Peak and trough concentrations The maximum and minimum drug concentrations achieved during repeated dosing cycles
Minimum effective concentration (MEC) The plasma drug concentration below which a patient’s response is too small for clinical benefit
First-pass effect, presystemic elimination The elimination of drug that occurs after administration but before it enters the systemic circulation (eg, during passage through the gut wall, portal circulation, or liver for an orally administered drug)
Steady state In pharmacokinetics, the condition in which the average total amount of drug in the body does not change over multiple dosing cycles (ie, the condition in which the rate of drug elimination equals the rate of administration)
Biodisposition Often used as a synonym for pharmacokinetics; the processes of drug absorption, distribution, and elimination. Sometimes used more narrowly to describe elimination

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EFFECTIVE DRUG CONCENTRATION

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The effective drug concentration is the concentration of a drug at the receptor site. In patients, drug concentrations are more readily measured in the blood. Except for topically applied agents, the concentration at the receptor site is usually proportional to the drug’s concentration in the plasma or whole blood at equilibrium. The plasma concentration is a function of the rate of input of the drug (by absorption) into the plasma, the rate of distribution, and the rate of elimination. If the rate of input is known, the remaining processes are well described by 2 primary parameters: apparent volume of distribution (Vd) and clearance (CL). These parameters are unique for a particular drug and a particular patient but have average values in large populations that can be used to predict drug concentrations.

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VOLUME OF DISTRIBUTION

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The volume of distribution (Vd) relates ...

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