Drug Absorption

Question 1

describe drug absorption

Answer 1

The process by which a drug moves from its site of administration to the systemic
circulation

Question 2

factors affecting oral absorption of drugs (physicochemical properties of a drug)

Answer 2

Molecular size - general rule: oral absorption decreases as molecular weight ↑
Solubility - hydrophilicity and lipophilicity affect passive diffusion at membranes
Ionisation - only unionised drug molecules can diffuse passively
across lipid membranes

Question 3

clinical application of drug absorption with examples

Answer 3

Activated charcol is porus allowing asprin drug molecules to become attached and then excreted in feaces. This impacts to absorption of asprin in the body during an overdose

Question 4

two approaches to estimate drug solubility

Answer 4

LogP
Polar surface area

Question 5

ATP-Binding Casette transporters

Answer 5

Active transport

Question 6

Solute Carrier transporters

Answer 6

facilitated diffusion and active transport

Question 7

naming three important ABC
transporters involved in intestinal efflux of drugs

Answer 7

MRP2 - multidrug resistance protein 1
BCRP - breast cancer resistance protein
MDR1 (multidrug resistance protein 1) or P-gp - P-glycoprotein

Question 8

Modes of drug absorption

Answer 8

Transcellular (move across cell)
- lipophilic drugs
- passive diffusion / facilitated diffusion (carrier proteins)

paracellular (through tight junction)
- low molecular weight and hydrophilic drugs

Question 9

Routes of administration of drugs

Answer 9

oral –> via the intestine
Intravenous
Inhalation
Intranasal

Question 10

LogP

Answer 10

1. Mix the drug with two layers of solvent - organic and water
2. Wait until the drug achieves equilibrium
3. Measure drug conc. in both layers
   LogP= log ([drug]oragnic/ [drug] water)
   Orally admisinterd drugs have a LogP value of <5

Question 11

Lipophilic Drug

Answer 11

High conc. in octane

Question 12

Hydrophilic Drug

Answer 12

High conc. in water

Question 13

Prodrug

Answer 13

Increases lipophilicity of drug –> increases absorption

Question 14

Polar surface area (PSA)

Answer 14

• the sum of surfaces of polar atoms in a molecule -
  usually N or O and attached H
• predict intestinal absorption, blood-brain barrier crossing

Question 15

TPSA (topological PSA)

Answer 15

calculate the sum of known surface contributions of
polar fragments

Question 16

factors affecting oral absorption of drugs (various biological factors)

Answer 16

o pH
o ingested food
o gut mobility
o intestinal enzymes
o transporters

Question 17

Caco-2 cells transport experiment

Answer 17

Experi 1:
- add drugs to apical side (gut wall)
- measure [drug] by taking a sample
from the basolateral chamber (B) at
defined time point(s)
- calculate apparent permeability Papp(A-B)
Experi 2:
- add drug to the basolateral chamber (capillary facing) (B)
- measure [drug] by taking a sample
from the apical (A) chamber at
defined time point(s)
- calculate apparent permeability Papp(B-A)

Question 18

three in vitro approaches to investigate transporter(s) involved in intestinal efflux of drugs

Answer 18

1. transporter knockout (KO) Caco-2 cell lines
2. cells transfected with transporter of interest
3. inhibitor of transporter of interest

Question 19

Calculating Efflux ratio

Answer 19

Calculate efflux ratio (ER) = Papp(B−A)/Papp(A−B)
- ER ≥ 2 indicates transporter-mediated drug efflux

Question 20

transporter knockout (KO) Caco-2 cell lines

Answer 20

Produce Caco-2 cell lines without 1 or 2 transporters to determine using the efflux ratio whether the remaining transporters contribute to the transport mediation

Question 21

cells transfected with transporter of interest

Question 22

inhibitor of transporter of interest