Skip to Main Content

++

INTRODUCTION

++

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).

++

“FRONT-END KINETICS”

++

Absorption

++

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.

++

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.

++

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).

++

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.

++

Distribution (Protein Binding, Compartmentalization)

++

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:

++

Vd = dose/concentration

++

Volume of distribution is an intrinsic ...

Want remote access to your institution's subscription?

Sign in to your MyAccess profile while you are actively authenticated on this site via your institution (you will be able to verify this by looking at the top right corner of the screen - if you see your institution's name, you are authenticated). Once logged in to your MyAccess profile, you will be able to access your institution's subscription for 90 days from any location. You must be logged in while authenticated at least once every 90 days to maintain this remote access.

Ok

About MyAccess

If your institution subscribes to this resource, and you don't have a MyAccess profile, please contact your library's reference desk for information on how to gain access to this resource from off-campus.

Subscription Options

AccessAnesthesiology Full Site: One-Year Subscription

Connect to the full suite of AccessAnesthesiology content and resources including procedural videos, interactive self-assessment, real-life cases, 20+ textbooks, and more

$995 USD
Buy Now

Pay Per View: Timed Access to all of AccessAnesthesiology

24 Hour Subscription $34.95

Buy Now

48 Hour Subscription $54.95

Buy Now

Pop-up div Successfully Displayed

This div only appears when the trigger link is hovered over. Otherwise it is hidden from view.