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Biopharmaceutics Notes
Pharmacy

Name:
Section: :
Date:

Pharmacokinetics

Pharmacokinetics vs Pharmacodynamics

Pharmacokinetics: How does the ____________________ as it ___________ through the different

______________ of your body.

Pharmacodynamics: How does the ____________ exerts its __________on your _____________.

Book Definition:

Pharmacokinetics: What the ___________ does to the ___________

Pharmacodynamics: What the ___________ does to the _____________

Pharmacokinetics (In) vs (Out)

Absorption The process of substance _________ the ___________ (___________) ____________

Distribution The ____________ of a ____________ throughout ___________ and _______ of the

___________.

Metabolism The ___________ _____________ of ___________ compounds into __________

compounds.

Excretion The _____________ of ____________ to the body

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Important Concept Before Proceeding to Absorption:

Formula:

Problem: A 10mg dose of drug X is 100% absorbed, what is the plasma drug concentration?

Case 1: I.V bolus + 1 Compartment (Plasma) + No Elimination

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Case 2: Oral Medication + 1 Compartment (Plasma) + No Elimination

Bioavailability
Definition: The ______________of administered dose that reaches the systemic circulation.

Main Determinants: 1. _______________ 2. ____________________

- Formula: Bioavailability (route) =

AUC= _______________________ proportional to the amount of drug absorbed

Keypoints:

Think of AUC IV as the amount of drug in plasma if ______________ had been absorbed
Think of AUC route as the _____________ of drug that gets into _____________

Problem: Metoprolol oral bioavailability is 50%. If the standard IV dose is 50mg what is the oral dose
should be? (our goal is to reach the same plasma concentration)

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A. Absorption

1. Transfer of drug from route of administration, across the _______________ into the
____________.
2. Cell membrane are ___________ in nature.

3. Factors that affect absorption

A.

B.

C.

Non-ionized chemicals are lipid soluble, while ionized (polar) chemicals are water soluble.
Because the cells mostly are made up of fatty molecules, it is principally the non-ionized, lipid
molecules that are able to penetrate the across the cell membrane.
Since most drugs are either weak organic acids (ex. aspirin) or weak organic bases (ex. codeine),
they undergo dissociation (ionization) in solution. The extent to which drug undergo ionization
depends upon the pH of the solution.

D.

E.

Outline of the major pathways of absorption, distribution, metabolism and excretion of drugs if
taken orally, intramuscularly and intravenously. Oral medications must pass through the liver
before proceeding to systemic circulation. In this process, drugs will be divided into 3: Free drug,
Protein Bounded Drugs and Metabolites, where the metabolites will be excreted via kidney.
Free drug will be deposited to the site of action of drug or where its receptor is located.

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 If drug is taken intramuscularly, drug will be deposited to tissue depot and later on diffuse to
systemic circulation.
Drug taken intravenously will be 100% bioavailable since it is directly injected to the bloodstream.

Distribution and Apparent Volume of Distribution

See Case 1 for Review (page 3)

Case 3: I.V bolus + 2 Compartments (Plasma and Extravascular Space) + No Elimination

Apparent Volume of Distribution

- Not a variable

- Some drugs like to stay in the plasma

- Have _________ Vd

- Some drugs like to stay in the extravascular compartments

- Have _________ Vd

- Helps you figure out how much total drug to give to reach your _____________

Factors to Determine Apparent Volume of Distribution

- ______________

- ______________

- ______________

- ______________

Examples of Apparent Volume of Distribution

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Apparent Volume of Distribution Comparison

Important Points

1. Why do we care about plasma concentration?

Distribution: From Theoretical to Practical Exercise

A person has a bacterial pneumonia. You decide to give erythromycin I.V. The minimum antibiotic plasma
concentration which will inhibit bacterial growth is 20mg/dl. The volume of distribution is 40L. What
should the IV dose be?

Absorption and Distribution: From Theoretical to Practical Exercise

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A person has a bacterial pneumonia. You decide to give erythromycin in an oral tablet form. The
minimum antibiotic plasma concentration which will inhibit bacterial growth is 20mg/L. The volume of
distribution is 40L and the oral bioavailablity is 25%. What should the oral dose be?

B. Distribution

1. The movement of the ______________ to the ___________.

2. Site of _____________ (______________)

3. __________________ (______________)

- Valium and similar drugs accumulates in the _________ cells.

4. _______________________ (BBB)

a. Many drugs, including systemic antibiotics, cannot usually across the BBB formed by the
_____________ surrounding the capillaries in the brain and spinal cord.

A. Benadryl

B. Loratadine

C. Hallucinogenic Drugs (Flasbacks)

5. Redistribution of Drugs to the Body

A. The action of some drugs is terminated, not by _____________from the body, but by
__________________

to another site of the body.

- Thiopental, _________________

1. Thiopental enters the brain rapidly due to its _____________________.

2. as the __________________ of Thiopental in the blood falls, the drug __________ out of the
brain , and begins moving in to _______________.

3. Thus, the _______________ duration of effect of the thiopental on the brain is due to the
_____________ of distribution of the drug from its ______________ (brain) to ________________.

First Pass Metabolism: Metabolism of a drug before it reaches the hepatic circulation

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Where the metabolism occurs?

Important: Pre Metabolism Discussion

OUTCOMES

C. Metabolism (___________________)

1. Occur mostly in the ________________

2. Metabolic reaction generally transform the drug into an ______________ and/or make it more
_____________ to facilitate _____________.

3. The transformed substance is called _________________

4. There are two main types of metabolic reaction

A. (____________) _______________ Reactions

1. ___________________

- _____________is incorporated to the chemical substance,

- _______________ of the ______________

- associated with enzymes such as _____________, ______________and

_____________that hydrolyze ____________, ___________and _____________.

- ___________ containing enzyme

- Backbone Reaction:

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 Most Common CYP ________ and _________ = _______, _________, _______

2. _______________

- ____________atoms are removed from the ___________ (OIL)

- _________________ (___________________ in ____________) oxidizes many

substances including ___________, ____________and _________________.

- Backbone reaction:

3. Reduction

- _______________are _____________from the molecule. (RIG)

4. Deamination

- _________________ are _______________ from the molecule.

B. Conjugation Reaction (Phase 2 Reaction)

-________________ join ______________ (an amino acid) to ____________,

____________ and _____________ that makes them ____________

5. Factors that affect the rate of the drug Metabolism

a. ____________
b. ____________
c. ____________

6. Life (T1/2) of Drug

The time it takes for the peak level of the drug in the bloodstream to fall by .

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Chemical Kinetics
- ______________ is the change in the _____________ of a ___________ or a ________ with
_______ (M/s).

- Represented by the _______

Rate Formula Starting Point:

Where do we get the Order of Reaction?

Application: Sample Problem 1

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Application: Sample Problem 2

Zero Order Reaction and its Half Life

First Order of Reaction and its Half Life

2nd Order of Reaction and its Half Life

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Clearance

- Is the volume of plasma that is cleared of drug per unit time

Key Points to Remember:

1. Definition of Clearance:

Units:

2. Clearance is ___________________ used to determine rate of elimination.

3.

4. Maintenance Dosage = Clearance (Desired Plasma Concentration)

Bioavailability

5. Maintenance Dosage = (Volume of Distribution) (Desired Plasma Concentration)

Bioavailability

Renal Excretion= Filtration Reabsorption + Secretion

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 D. Excretion

1. Kidneys
a. Glomerular Filtration
i. About ___________ of the blood flowing through the ____________ (Renal
blood Flow) is filtered into the _____________ of the kidney.
b. Tubular Reabsorption
i. Essentially all the ____________ form of drugs that has entered the renal
tubules passes into the ______________ and is excreted in the urine.
ii. About ____________ of the ______________ of a drug that has entered the
___________ passively diffuses right back into the ____________ (via
peritubular capillaries), so that the only of the ____________ of the drug
passes into the _______________ collecting ducts and out in the urine
c. Tubular Secretion of weak organic acid

d. Tubular Secretion of weak organic base

e. Effect of Kidney Disease

2. Biliary Secretion
Drug Principal route of excretion
Penicillin
Erythromycin
Acetaminophen
Codeine

3. Lungs
a.
b.
4. Sweat and Saliva
a.
5. Mothers Milk
a.

Pharmacodynamics

A. Time course of drug effects

a. Onset of ___________ is affected by:
i. _________________
ii. _________________

b. Duration of action is affected by:

i. ______________
ii. _______________
iii. ________________
iv. ______________

Note: consider the ___________ of _____________

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Mechanism of Drug Action:

Clinical Principle: Drugs affect the physiological process within cells; they do not produce any _____
actions within the body.

1. Drugs that act on specific receptor site

a. Called ______ molecules (or ______________)
b. Drug-receptor site interaction is affected by:
i. ___________of the drug
ii. ___________ activity
1. The ____________ to cause an effect after binding.
2. ____________ (__________)
iii. Activation of Receptor Site
1. ___________ and ________ Ion Channels (Proteins)
2. __________up or ____________down transporters (Proteins)
3. __________ or ____________ enzyme activity

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 iv. Blockers (______________)
1. Drugs that possess affinity but no intrinsic activity
2. Drugs that ______ act on __________ receptor sites
a. Act to ___________ interfere with cell function
i.
ii.
iii.

Examples of Agonists and Antagonists

2. Dose-Response Effect Relations

a. As the doses increases, responses increases
b. Intrinsic activity (Efficacy)
c. Potency
i. The amount of a drug needed to produce a given effect
ii. Potency is both determine by both the drugs affinity and intrinsic activity

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 3. Biological variation in response
a. ED ____
i. Therapeutically effective dose in ___________ of the _________.
ii. This average effective dose is normal expressed for a ______ (70kg) _________

b. Calculation of drug dosage using ______ Rule:

Weight (lb) X Adult Dose = Infant Dose

150

An cancer patient infant weighs 50 pounds is in need of codeine daily dosage. The usual dose of the
codeine is 60mg. Compute for the dosage appropriate for the infant.

c. Factors that may require adjustment of calculated drug dosage:

i. Age of Patient
ii. Gender of Patient

d. Pre-existing pathologic states

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 i.
ii.

e. Physiological Factors
i. Placebo Effect
ii. Stress and emotional state

f. Drug Tolerance (Tachyphylaxis)

i. Repeated use of drugs (Lowering of _________ ) = Decrease of response
(________)
ii. Due to ________ and __________ adaptation to the drug

g. Drug to Drug Interactions

i. Concurrent use of more than 1 _________ may necessitate adjustment of drug
dosages.
ii. Example:

Drug Metabolism
Enzyme Induction:

Enzyme Inhibition:

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Intestinal P-glycoprotein:

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