BIOPHARMACEUTICS AND PHARMACOKINETICS
Drug apparently distribute more rapidly in
Once the drug begins to be absorbed it
undergoes various transports processes which
delivers it to the body areas away from the
absorption sites, this transport processes are
collectively referred to us DRUG
DISTRIBUTION.
This is evidence by the constant changing of
drug to various body tissues and fluids
For most drug distribution throughout the body
occurs mainly at blood flow through the organs
and tissues. However many factors affect
distribution.
To understand the distribution of the drug
characteristics of different tissues must be
considered.
Context clue is PERFUSION/BLOOD FLOW
Highly perfused organs rapidly attain drug
concentrations approaching those in the plasma
particularly part of the central compartment
Less perfused or the poorly perfused organs
this tissues take such time to attain drug
concentrations
REMEMBER (PERFUSION LIMITED
DISTRIBUTION)
areas with higher blood flow.
If the blood flow increases the rate of
distribution of the drug in tissue increases
REMEMBER (PERMEABILITY-LIMITED
DISTRIBUTION)
This is because of barriers (anatomic barrier)
We all know that the cell membrane or the
plasma membrane is composed of lipid
bilayer (pwede lang makadaan ay mga lipid
soluble drugs) because of the principle LIKE
DISSOLVES LIKE that’s why polar drugs or
the water soluble drugs they have limited
capability of distribution of crossing the lipid
bilayer of the cell membrane (LUNA).
TAKE NOTE:
Absorption has the same characteristics with
distribution.
Sino ang mga hindi mag uundergo ng drug
distribution?
WIPE because they are not absorbed
Example: blood brain barrier (BBB) limits the
entering of drug into central system from the
bloodstream.
If ionized there is a limited distribution in the
central nervous system and for those drug
with high molecular weight
BBB only allows drug that is lipid soluble and
very small molecular weight (example of
anatomic barrier.
 BIOPHARMACEUTICS AND PHARMACOKINETICS
After the drug begins the distribution in the
tissue concentration increases until it reaches
an equilibrium
Plasma concentration is particularly in the
blood/central compartment or the highly
perfused organs while Tissue concentration
is represented by the peripheral compartment
(the concentration in the tissue increases after
the drug is administered it is readily flows to
the central compartment and then the
concentration in the tissue increases until it
reaches equilibrium (the amount of the drug
entering and leaving the tissue are the same)
The drug concentration in the tissue at
equilibrium depends on the plasma drug
concentration and the rate in which the drug
distributes.
In tissue in which drug distribution is slower
(ex. Fat tissue reaching equilibrium may take
much longer
Saan nakadepende yung rate of
distribution?
BLOOD FLOW/PERFUSION.
Another major factor affecting drug distribution
is the effect of the various disease state in the
body physiology
Napaka Importante ng cardiac output (it is
the volume of blood pumped by the heart
in each minute) so if there is low Co means
lesser blood pressure.
TAKE NOTE
A decrease of blood perfusion in the
tissues results in lower rate or what we call
slower rate of distribution or the lower drug
concentration in the affected tissues relative in
the plasma drug concentration
In the tissue that receives poor distribution is
the primary elimination organ
Ex. kidney if mababa ang kanyang cardiac
output na re recieve or mababa ang perfusion
a lower rate of drug elimination occurs.
The drug may accumulate in the body. This
occurs in those tissues or organs that are
primarily eliminating organ. The drug may
cause toxicity. RENAL DOSING ons of the
most important clinical pharmacists skill
particularly in those patients with kidney
failure or chronic kidney disease. Because it
provides a correct dose to patients with renal
failure to avoid any accumulation and any
toxicity
For the drug that is highly lipid soluble
LUNA easily penetrates most membrane
barriers that is mainly lipid based kasi nga the
membrane barrier natin usually composed of
lipid bilayer. Therefore it also undergoes rapid
distribution particularly to fat tissue (the
principle is LIKE DISSOLVES LIKE.
So if the drug is highly soluble mabilis siyang
makapenetrate kaya mabilis din siyang
maidistribute sa mga lipid based tissue din
 BIOPHARMACEUTICS AND PHARMACOKINETICS

particularly fat tissue. Due to the nature of biologic membrane drugs

that are unionized, uncharged and has
And in the other hand if the drug is highly lipophilic or fat soluble property are most likely
polar
to crossed most barriers. LUNA
WIPE
Hydrophilic this drugs do not distributes well in
the fat tissue because the drug is readily
eliminated

After the drug is absorbed it is distributed to

The pH is neutral or slightly basic
If ionized it will not be readily absorbed
One example of this phenomenon is the
excretion of the drug in the breast milk
Remember
Only an ionized drug can passed through lipid
membranes
Unionized pwede pumasok sa lipid
membranes
Ex. alkaline drugs are particularly unionized at
7.4 pH (slightly basic)
Sino yung uniozed sa pH 7.4? Yun yung
tinatawag nating alkaline drugs
Alkaline that is mostly unionized that has a
physiologic pH of 7.4 can pass through the
lipid membrane of the breast tissue. However
once inside the breast tissue the alkaline drug
become ionized (bakit magiging ionized
yung gamot) it is because the milk is acidic,
kaya nung pumasok siya ang unionized and
when the alkaline in the breast tissues na
merong milk that is acidic it becomes ionized.
The drug becomes trapped in the breast
tissue and hindi na siya mag uundergo ng
distribution because the drug now is ionized
and it is now readily excreted via milk. This
phenomenon is also applicable in the urine
(which is the ion trapping
the blood or the systemic circulation and here
we have two types of drugs
1. Free drug-you can interact with a
receptor there is an drug effect in the
site of action there is a
PHARMACOLOGIC RESPONSE
It distributes freely, drug binding is
rapidly reversible and can undergo
dissociation or association.
THE PROCESS IS CONTINUOUS kapag
kailangan ng free drug.
Pag sumobra ang free drug undergo
association to become bound drug
2. Protein drug (bound drug)
Theoretically drugs that are bound to plasma
proteins are not pharmacologically active
(INACTIVE) the protein-bound drug should
undergo dissociation to become FREE DRUG
which is the only pharmacologically (ACTIVE).

REMEMBER
 BIOPHARMACEUTICS AND PHARMACOKINETICS

This illustration as you can see gives you a

percentage of drugs bound to plasma proteins
and the phenytoin has the highest affinity to
plasma protein

Top 1 more than 90% is bound to plasma protein

NSAIDS madalas.
Such as
● Aspirin
● Indometacin A major contributor to this variability is the
● Phenylbutazone presence of a disease or altered physiologic
Mga usual na 80-90% protein bound drugs state which can affect plasma concentration or
● Phenytoin the affinity of the binding proteins.
● Warfarin
● Valproic acid Ex.
Remember Pag mababa daw si albumin concentration
If there is two drugs highly protein bound drugs pag may mga sakit ka na hepatic or renal may
there is a phenomenon that can occur pag tendency na tumaas yugn free drug kasi kunti
pinagsabay mo silang itake if there is a yung albumin (pag kunti yung albumin tendency
concumitant administration of drug kukunti yung bound drug and madami na
(DISPLACEMENT) ngayon si free drug (there is abnormally free
drug) pag masyadong marami si free
pharmacologically active yun.

If there is too much active drug that can lead to

1. Albumin has the highest concentration
among the plasma protein they are
bound usually with anionic and cationic
na tinatawag nating acidic drugs
2. Alpha 1 acid glycoprotein has the
second highest concentration that is
bound to cationic na tinatawag nating
mga basic drugs.
3. Lipoproteins they are bound to lipophilic
drugs
REMEMBER
That a bound drug INACTIVE.
toxicity.
Kaya pag may mga hepatic or renal we need to
reduce the dose to prevent or avoid toxicity
.Mataas si alpha-1-acid glycoprotein there is
abnormally high bound drug magiging kunti si
free drug there is an insufficient amount of active
drugs that majority that are available are inactive
then there is a sub therapeutic effect that the
patient can have experience so ang gagawin
natin we could have increase the dose
And if there is a concomitant administration of
displacer drug or the displacement drug
Ex. salicylic acid and valproic acid and NSAIDs
this are commonly administered with another
drug this agents may display the drug of interest
leading now to what we call toxicity

Ex.
ASA will displace warfarin to albumin at ang free
drug ni albumin then 10% lang ang free drug ni
 BIOPHARMACEUTICS AND PHARMACOKINETICS

warfarin and pag nadisplace si warfarin to

albumin tendency dadami ang free drug which is
more than 10% and an excess free drug can
lead to toxicity kasi too much active drug is
within the site of action that causes hemorrhage
or what we call bleeding (pwedeng mamatay
because of internal bleeding)

Another example
Digoxin and quinidine 1. VD=Vp + Vt (Fp/Ft)
Pag pinagsabay mo silang dalawa this drug are We would use this as the formula for this
primarily bound to alpha-1-acid glycoprotein example
VD=5L + 80L (0.1/0.2)
VD=45L (whole body fluid or WBF)
2. VD=5L + 80L (0.1/0.2)
Displacer is quinidine and would make digoxin VD=85L (deep tissue)
toxic Last step is to determine where is the drug
particularly

This can be computed with pharmacokinetic Whole body weight is 70kg=70L

model If more than it is found in the deep tissue
Remember
VD=Xo over the Co at time 0
But now the physiologic model
If we said critical component it is the
consequences of protein binding (we consider
the protein binding)
Consequences of protein binding changes in the
volume of distribution can be implied using the
physiologic volume of distribution
VD=Vp + Vt (Fp/Ft)
If the two fraction are the same it is negligible
and pag same lang add mo na yung dalawa na
Vp and Vt and that would be the volume of
distribution.