MOVEMENT OF DRUG MOLECULES:
LIPOPHILIC VS. HYDROPHOLIC
• HYDROPHILIC drugs travel well in aqueous environments.
• They are either polarized or ionized, allowing them to interact well with water
molecules, which will dissolve them.
• LIPOPHILIC molecules travel well across the phospholipid bilayer of the cell membrane.
• They are nonpolarized and nonionized.
• All of the drug molecules in a medication do not have to exist in the same form
(hydrophilic/lipophilic) as they travel through the body. A drug can exist as a ratio of
hydrophilic (ionized) molecules to lipophilic (nonionized) molecules.
• Hydrophilic molecules can become lipophilic and vice versa
• Pharmacokinetics studies how drug movement and
concentrations in the body are affected by physiology
or drug characteristics.
• Absorption, distribution, metabolism, elimination
ABSORPTION
AND
BIOAVAILABILITY
• All can be altered by disease or physiologic conditions. This
can affect the drug dose that the animal needs.
• ABSORPTION: the movement of drug molecules from the
site of administration to the systemic circulation. Rapid,
total absorption of the drug is desired unless the drug acts
locally (topical).
• BIOAVAILABILITY: the degree to which an administered drug
is absorbed
EFFECT OF ROUTE OF
ADMINISTRATION ON ABSORPTION
• Route of administration directly affects the drug’s bioavailability and rate of absorption.
• IV route skips the absorption phase since the drug is placed directly into the circulatory
system. The bioavailability is 1.
• IM drugs are absorbed rapidly and almost completely so bioavailability is only slightly less
than 1.
• SQ and PO drugs have a bioavailability significantly less than 1.
• If a drug is absorbed rapidly, it will rapidly have high plasma concentrations. Signs of toxicity
could show at this time. A slowly absorbed drug (oral or SQ) will take more time for its
plasma levels to peak and will do so at a lower blood concentration.
EFECT OF LIPOPHILIC AND HYDROPHILIC
PROPERTIES ON ABSORPTION
• Whether a drug is hydrophilic or lipophilic can affect the drug's ability to dissolve in
water or pass through a cell’s membrane.
• The environment that the drug is placed plus the form or the drug
(hydrophilic/lipophilic) affects absorption.
• SQ or IM drugs are placed in extracellular fluid when injected. They must diffuse through the
fluid to get to the circulation.
• A drug with molecules predominantly in the hydrophilic form will be more rapidly absorbed
SQ or IM than drugs that exist primarily in the lipophilic form.
• PO drugs must pass through cellular membranes to be absorbed through the lumen of the
GI tract.
EFFECT OF PH OF THE ENVIRONMENT ON
ABSORPTION
• The ratio of hydrophilic to lipophilic drug molecules in a medication can be affected
by the pH of the environment that the drug is in. This ratio can change as the drug
moves through different environments.
• Chart on page 59
• The characteristics of drugs that determine their ratio of ionized to nonionized
molecules at any given pH are the drug's acid/base nature and its pKa.
ACID DRUGS VS. ALKALINE DRUGS
• The acid or base nature of a drug molecule determines the shift in a drug’s hydrophilic
or lipophilic form as the environmental pH surrounding the drug changes.
• An acid drug has a chemical structure that causes it to release a hydrogen ion into
the liquid environment as the drug is placed in increasingly alkaline environments.
• By releasing a hydrogen ion, the drug becomes ionized as it now acquires a charge.
• An acid drug becomes more hydrophilic as it is placed into a more alkaline environment.
• As an acid drug is placed in an increasingly acidic environment, the drug will exist more in
the lipophilic form.
• Basic drugs behaves in an opposite manner. They become more hydrophilic as they
are placed in an increasingly acidic environment and more lipophilic as they are
placed in increasingly alkaline environments.
PKA
• pKa of a drug is defined as the pH in which the ratio of a drug‘s ionized to nonionized
molecules is 1:1.
• Knowing whether a drug is an acid or a base and knowing its pKa will allow someone
to know which form (hydrophilic or lipophilic) that drug will exist in at any pH.
• The ratio of ionized to nonionized molecules can be more precisely determined of the
drug’s acid/base nature, its pKa, and the environmental pH are known.
• Acid drugs become more lipophilic at pH values to the acidic side of a drug's pKa,
whereas basic drugs become more lipophilic at pH values to the alkaline side
ION TRAPPING AND ABSORPTION OF
DRUGS
• The many compartments of the body have different pHs.
• As a drug molecule passes to different compartments with varying pHs, the ratio of
ionized to nonionized molecules changes.
• A drug molecule in the lipophilic/nonionized form crosses a cell membrane and enters
a new body compartment whose pH causes the molecules to shift to
hydrophilic/ionized. This molecule may now be trapped in their new environment
because lipophilic/nonionized is the form that crosses the membrane easily.
• The state of this molecule being “stuck” in the cell is called ION TRAPPING.
ION TRAPPING AND ABSORPTION OF
DRUGS
• Ion trapping example
• Aspirin is an acidic drug. When aspirin is in the acidic environment of the stomach, it exists
predominantly in the nonionized/lipophilic form. Aspirin will easily enter the cells of the
stomach. The inside of these cells have a pH of 7.4. Most of the drug molecules will shift to
the ionized/hydrophilic form in this pH, which will “trap” those molecules inside the cells.
• There will always be some nonionized/lipophilic molecules inside the stomach cells
(remember, at a pH of 7, the ratio of ionized/nonionized aspirin molecules is 10,000:1. As a
nonionized/lipophilic molecule leaves the stomach cell and enters the circulatory system,
an ionized/hydrophilic molecule is converted to the nonionized/lipophilic form to preserve
the ratio. This action continues until all aspirin molecules have exited the stomach cells and
entered the circulation.
EFFECT OF DISSOLUTION AND GI MOTILITY
ON ABSORPTION OF ORALLY ADMINISTERED
DRUGS
• Oral medication must be in the lipophilic form to be absorbed into the cells of the GI
tract. The medication must also be small enough to enter the cells.
• The form of oral medication (solid vs. liquid) also has an effect on the absorption of the
drug.
• DISSOLUTION is the dissolving of a drug.
• Liquid medications (solutions, elixirs) do not have to go through a dissolution process.
• Solid medications (tablets, granules, powders) must go through dissolution and be broken
apart to be absorbed.
• Because liquids do not have to go through dissolution, they are usually absorbed more
rapidly than solid forms of medication and may have a quicker onset of action.
EFFECT OF DISSOLUTION AND GI MOTILITY ON
ABSORPTION OF ORALLY ADMINISTERED DRUGS
• Sustained-release tablets dissolve slowly over minutes to hours, releasing small amounts
of medication for absorption and sustaining a consistent level of medication in the
blood.
• Because the medication is released slowly, there will be a lower peak in blood
concentration of the medication than if it were given in a regular-release form.
• Medication that causes a high peak in blood concentration will move out of the blood and
into the body’s cells quickly, as it happens via diffusion.
• The higher the peak in blood concentration, larger the concentration gradient between
the blood and tissues.
• The larger the concentration gradient, the quicker the diffusion will happen into the tissues.
EFFECT OF DISSOLUTION AND GI MOTILITY ON
ABSORPTION OF ORALLY ADMINISTERED DRUGS
• Most absorption for PO drugs occurs in the small intestine, so dissolution needs to occur
before the meds get there.
• Alteration of the GI tract’s motility can effect how much time a medication has to
dissolve and be absorbed.
• Conditions or diseases that decrease gastric motility can delay movement of drugs into the
intestines and delay absorption and onset of action of orally administered drugs.