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INTRODUCTION

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Pharmacokinetics describes the body’s response to administration of a drug, which determines drug absorption, distribution, and elimination. An easy way to make sense of this elusive topic is to think of pharmacokinetics in the simplest terms: drug goes in (front-end kinetics) and drug goes out (back-end kinetics).

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“FRONT-END KINETICS”

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Absorption

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Most drugs in the perioperative period are given intravenously, thus bypassing the pharmacokinetics of absorption. Drugs injected directly into vasculature are not impacted by absorption pharmacokinetics; however, drugs administered by oral administration, transmucosal delivery, transdermal delivery, or tissue injection have variable absorption rates. Even inhaled anesthetics are absorbed through the lungs, typically by very rapid transport. Bioavailability is the relative amount of a drug dose that reaches the systemic circulation unchanged and the rate at which this occurs.

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The key concept of absorption is transfer from the depot to the systemic circulation. The depot refers to the organ system where the drug gets deposited: stomach, lung, nerve bundle, transdermal patch, and muscle tissue. This transfer is principally driven by the concentration gradient but can be affected by intrinsic properties of the drug that are specific to the route of administration.

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Diffusion for the depot to systemic circulation occurs through a bilipid membrane; therefore, the physical properties of the drug play an important role in the rate of absorption. Small, nonpolar molecules pass easily through a bilipid membrane that contains a large hydrophobic central region and a small hydrophilic surface. Therefore, the pKa of a drug relative to physiologic pH will determine polarity of the molecule. In addition, diffusion of drug across a membrane is directly proportional to the concentration gradient between the depot and the system circulation (first-order kinetics).

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The absorption of inhaled anesthetics depends on the blood–gas partition coefficient. This physical property of inhaled anesthetics describes its concentration in the blood compared to that in the alveolar gas at equilibrium. For example, if the concentration of a drug in blood is 10 and its concentration in alveolar gas is 5, its partition coefficient is 2. A high blood–gas partition coefficient means that a large amount of drug must be absorbed before equilibrium occurs. Clinically, this means that it will take longer for the desired effect to be achieved. Partition coefficients are temperature dependent.

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Distribution (Protein Binding, Compartmentalization)

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Distribution describes the process of dilution from very high concentration at the entry point of the drug (IV site, mucosal lining of the stomach, site of subcutaneous injection, etc) to the relatively low concentration in plasma and other tissues. Distribution of a drug is discussed in terms of volume of distribution (Vd), the volume of tissue that the drug “reaches,” which can be calculated by the following equation:

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Vd = dose/concentration

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Volume of distribution is an intrinsic ...

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