BIOPHARMACEUTICS AND PHARMACOKINETICS

Name: DABU, NICHOLE R. Date: 24 OCTOBER 2021

Section: BSPH 2Y1-2 Score: _________________

Exercise No. 2
TRANSPORT PROCESSES

Drugs permeate at the site of absorption towards the systemic circulation and into its target site
of action before eliciting its therapeutic activity. For drug to be absorbed into the systemic
circulation, it must first cross the cell membrane. This process is highly dependent on the
physicochemical property of the drug and certain specific biochemical properties of the cell
membrane. The integrity of the cell membrane may pose a significant barrier to drug delivery.
Different transport processes are identified by which specific drugs, according to their
physicochemical properties cross the cell membrane. These are passive diffusion, convective
transport, active transport, facilitated transport, ion-pair transport and pinocytosis.

1. Enumerate and discuss the different transport mechanisms of drug absorption. Give at least
two (2) examples of substances or drugs transported by these mechanisms. Illustrate the
movement of these drugs across the cell membrane through different transport mechanisms.

Transport Mechanism Properties Example of substances

transported through this
process

The spontaneous diffusion of ● organic acids

Passive Transport
Carrier Mediated Transport
→ Active Transport
→ Facilitated Transport
molecules from an area of
higher concentration to a ● cardiac glycosides
region of lower concentration,
doesn’t need an external
energy.
Active Transport Active Transport
 Is a carrier-mediated ● 5-FU (5 Fluorouracil)
transmembrane
mechanism that is ● Testosterones
involved in the
absorption, renal, and
biliary secretion of
several medicines and
metabolites in the
gastrointestinal tract.
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Convective Transport
Facilitated Transport
 It's a carrier-mediated Facilitated Transport
transport as well, but it ● Vitamin B12
moves down a gradient
and doesn't require any
energy. For drugs, it is
saturable and
structurally selective.
Also called as Pore ● Ionized sulfonamides
Transport refers to the ability
of very small molecules to ● Inorganic and organic
pass cell membranes quickly, electrolytes up to 150 to
as though the membrane 400MW
contained channels or pores.

Phagocytosis Phagocytosis
Vesicular Transport  It is the engulfment of ● Cells
→ Phagocytosis bigger particles or
macromolecules that ● Cellular debris
→ Pinocytosis are ingested by
macrophages.

Pinocytosis Pinocytosis
 Cellular process that ● Ferritin and Insulin
allows fluid to be
actively transported ● Sabin polio vaccine
from outside the cell
through the cell's
membrane and into the
cell's interior.

Used to improve the ● Quaternary ammonium

permeation of ionized compound
Ion Pair Transport medicines that are
administered topically. ● Sulfonic acids

2. Discuss the Fick’s Law of diffusion and its significance in drug transport.

 Passive diffusion is generally governed by Fick’s Law of Diffusion

dQ = - DKA (Cp - Ct)
dt h
→ It relates the drug diffusion (dQ/dt), to the difference of drug concentration in plasma
(Cp) and in the tissue (Ct), the surface area of membrane (A), and the thickness of the
membrane (h).The negative sign denotes net transfer of drug from inside the capillary
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lumen intro the tissue and extracellular spaces. Diffusion is spontaneous and temperature
dependent.

3. Compare the different features of the stomach and the intestine and relate each in drug
absorption.

→ Stomach
● Basic drugs are solubilized rapidly in the presence of stomach acid.
● Absorption of oral drugs does not start immediately due to the stomach-emptying time.
● Enteric coated drug medications release the drug in the stomach due to the high pH of
stomach, thus it can cause irritation to the stomach.

→ Intestine
● The most important site for drug absorption, particularly the duodenum area.
● If a medicine is absorbed in the small intestine, it enters the hepatic portal vein via the
mesenteric arteries and travels to the liver before reaching the systemic circulation.
● Due to anatomic features such as villi and microvilli that give a wide surface area, the
duodenal portion of the small intestine demonstrates the maximum drug absorption.

4. Discuss how the following affects absorption:

a. Surface area of the absorption site

 In comparison to the stomach, the ileum has much greater absorptive surface area d/t villi
and microvilli. As a result, a drug's absorption rate from the intestine will be higher than
from the stomach.
 ↑ gastric emptying-> ↑ drug absorption
 presence of good in stomach dilutes the drug and slows gastric emptying-> ↓ drug
absorption

b. Degree of perfusion of the absorbing surface

 rates may increase absorptive surface area. rapid perfusion might reduce intestinal
absorption
 ↑ blood flow to intestine than stomach-> ↑ absorption from intestine than stomach

c. pH of the absorbing environment

 Weak acids tend to be absorbed in acidic environments, like the stomach.
 Weak bases tend to be absorbed in basic environments, like the duodenum
Thus, Drugs that are weak acids will be absorbed better than weak base drugs.

c. Gastric emptying time and Gastric emptying rate

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 Delay in gastric emptying time for the medicine to reach the duodenum slows the rate
and possibly the degree of drug absorption, extending the drug's onset time
 Increasing the rate of gastric emptying and gastro-intestinal motility enhances the rate
of medication absorption, while higher gastrointestinal motility is related with a decrease
in the rate of absorption for other drugs, such as digoxin and riboflavin.

5. State how transporters are involved in the absorption, distribution and elimination of drugs.
 ABSORPTION  P-glycoprotein has a definite role in reducing permeability across the
gastrointestinal system when it comes to absorption. As a result, partial, variable, and
non-linear absorption affects a wide range of medications.

 DISTRIBUTION  Transporters limits the drug distribution to tissues responsible for

their effect and/or toxicity, and transporters govern the pharmacological and/or
toxicological effects of medicines.

 ELIMINATION  Because of uptake and efflux transporters are found in organs

involved in drug biotransformation and excretion, they play a unique gatekeeper role in
regulating drug access to metabolizing enzymes and excretory pathways.

6. What is a placebo? Discuss the significance of placebo in assessing the therapeutics effects of
many drugs.
 A placebo is frequently included to demonstrate that the treatment are effective and
that the study is sensitive enough to detect the clinical effect in the study's patient
population. The test and reference products' superiority over the placebo is likewise
assessed using the same dichotomous outcome of "therapeutic cure." For safety
considerations, the use of placebo may not be used in some studies.

7. What are the determinants for drug liposolubility?

 The drug's lipophilicity is determined by the drug's distribution between the
aqueous and hydrophobic phases (such as 1-octanol).

 Chemical nature of the molecule

 Atomic or molecular formula weight (directly proportional to size)

 Valence or charge (polar versus nonpolar)

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References:

L. Shargel., Applied Biopharmaceutics and Pharmacokinetics. 7th Edition

Nimmo W. S. (1976). Drugs, diseases and altered gastric emptying. Clinical pharmacokinetics,
1(3), 189–203.

SAGE Journals: Your gateway to world-class research journals. SAGE Journals.

https://journals.sagepub.com/action/cookieAbsent

Editor. (2011, September 4). Factors affecting Absorption of Drugs. HowMed.

http://howmed.net/pharmacology/factors-affecting-absorption-of-drugs/
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DABU, Nichole R. 30 October 2021

BSPH 2Y1-2

ASS 4: Drug Distribution

1. Define Drug Distribution


2. Enumerate the distribution sites in the body. 
3. Define Protein binding
4. Enumerate the major proteins available for binding. 
5. Explain Drug affinity and its role in Drug displacement. 
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