F1 Pharmacokinetic parameters

Question 1

define absorption

Answer 1

movement of drug from the site of administration to the site of measurement

Question 2

define distribution

Answer 2

reversible transfer of drug within body

Question 3

define metabolism

Answer 3

loss of drug from body by chemical conversion

Question 4

define excretion

Answer 4

loss of unchanged drug from body

Question 5

define elimination

Answer 5

• irreversible loss of drug from body
• (metabolism + excretion)

Question 6

define disposition

Answer 6

• processes of elimination and distribution
• (distribution + metabolism + excretion)

Question 7

what 5 things will affect absorption?

Answer 7

movement across membranes
passive diffusion
lipophilicity (partition coefficient)
size
ionisation

Question 8

describe and explain how size will affect absorption

Answer 8

• very small water-soluble drugs can pass between cells (paracellular route)
• size affects passive diffusion too

Question 9

describe and explain how movement across membranes will affect absorption

Answer 9

if a molecule didn’t cross membranes, it wouldn’t have the potential to be a drug

Question 10

describe and explain how passive diffusion will affect absorption

Answer 10

Fick’s First Law

Question 11

describe and explain how lipophilicity will affect absorption

Answer 11

• lipid soluble drug = high permeability
• polar ionised compound = low permeability

Question 12

describe and explain how ionisation will affect absorption

Answer 12

• drugs: weak acids or bases
• pH affects ionisation and lipophilicity

Question 13

what is bioavailability?

Answer 13

• important term related to absorption, but not only absorption
• the fraction of the dose which reaches the systemic circulation as intact drug
• less than 100% in most cases

Question 14

causes of reduced oral bioavailability

Answer 14

• loss in faeces
• decomposition in the lumen
• destruction within the wall of the GIT (intestinal first-pass metabolism)
• destruction within the liver (hepatic first-pass metabolism), happens after absorption

Question 15

what happens when drug is carried by blood?

Answer 15

• it is reversibly transferred to tissue and back to blood
• equilibrium is reached with time but it is not a true equilibrium as drug is also lost from the body

Question 16

many factors affect the rate and extent of drug distribution. what are rate and extent in terms of distribution?

Answer 16

rate
- how quickly equilibrium is established between tissue and blood

extent
- how much drug is in tissue and how much is in blood

Question 17

what are the 2 major independent pharmacokinetic parameters?

Answer 17

volume of distribution
clearance

Question 18

describe volume of distribution

Answer 18

• it is not a real volume so is sometimes called apparent volume of distribution
• describes the relationship between the amount of drug in the body and the concentration in blood plasma

Question 19

what is a major determinant of volume of distribution?

Answer 19

the relative strength of drug binding to tissue components as compared to plasma proteins

Question 20

what are the 2 main routes of drug elimination?

Answer 20

• kidneys (mostly) = excreted unchanged
• liver (mostly) = metabolised and then excreted

Question 21

where can metabolism and excretion occur?

Answer 21

all over the body

Question 22

what are the most highly perfused organs in the body?

Answer 22

kidneys
liver

Question 23

what does clearance describe?

Answer 23

• efficiency of irreversible elimination of a drug molecule from the systemic circulation
• may be through excretion of the unchanged drug or metabolic conversion to a different molecule (metabolite may still be in the body but the parent molecule has been cleared)

Question 24

is uptake into tissues classified as clearance?

Answer 24

no, not if the unchanged drug eventually returns to the systemic circulation

Question 25

what is clearance defined as?

Answer 25

the volume of blood cleared of drug per unit time

Question 26

what can clearance relate to?

Answer 26

a particular organ or the whole body

Question 27

the clearance of a new drug by the liver may be 60 L/hr but the liver blood flow is 100 L/hr. what does this mean?

Answer 27

use of extraction ratio needed

Question 28

how could elimination of a drug from a body by an organ be achieved?

Answer 28

- excretion (in bile, in urine) - biotransformation (metabolism)

Question 29

what can the extraction ratio of the liver or kidneys be viewed as?

Answer 29

the organ's relative efficiency in eliminating the drug from the systemic circulation over a single pass through the organ

Question 30

what values can extraction ratio take? what do these values mean?

Answer 30

- any between 0 and 1 - if E = 1, complete extraction - if E = 0, no extraction

Question 31

what is the formula relating clearance (CL), extraction ratio (E) and blood volume (Q)?

Answer 31

CL = Q x E

Question 32

how can clearance be described in terms of?

Answer 32

in terms of the eliminating organ - hepatic clearance - renal clearance - pulmonary clearance in terms of the elimination process - metabolic clearance - excretory clearance

Question 33

for most drugs, what is the rate of elimination directly proportional to?

Answer 33

drug concentration in plasma

Question 34

what is the formula relating plasma drug concentration, clearance and rate of elimination?

Answer 34

rate of elimination = clearance x plasma conc

Question 35

what does elimination rate constant depend on?

Answer 35

clearance and volume of distribution

Question 36

what are clearance and volume of distribution as parameters?

Answer 36

- independent - they don't depend on each other

Question 37

what is the elimination rate constant (k)?

Answer 37

- a proportionality constant - proportion of drug in the body eliminated per unit time (usually per hour)