Pharmacokinetics & Biopharmaceutics

Question 1

Pharmacokinetics def.

Answer 1

The action of the body on a drug

ADME - determines the API conc in the body

Question 2

Biopharmaceutics def.

Answer 2

How the physiochemical properties of a APIs, dosage forms affect rate & extent of action

Question 3

Bioavailabilty def.

Answer 3

% of administered dose that reaches systemic circulation

Systemic circulation of oral dose from GIT)/(systemic circulation of IV dose

Question 4

Poor bioavailabilty

Answer 4

Requires: large dose - expensive, inconvenient

Potential for large Cp variation

Question 5

Pharmaceutics role

Answer 5

Design forms that: give desired profile
Not affected by patient variation
Safe/convenient
Stable
Minimise gastric side effects (irritation)

Question 6

Absorption site: stomach

Answer 6

Food causes increased residency time, slower absorption
Minimal absorption
Acidic pH

Question 7

Absorption site: Small intestine

Answer 7

Large SA - folds of Kerkring, villi, microvilli
Major absorption
Hours residency
Neutral pH

Question 8

Absorption site; Large intestine

Answer 8

Minor absorption
neutral pH
very long residency
Heavily colonised by bacteria

Question 9

Passive diffusion

Answer 9

Ficks law
Requires gradient
WAter solube requires pores, lipid soluble through membrane
Bigger gradient - larger flux
Sink conditions - GRadient retained by blood movement

Question 10

Fick’s law

Answer 10

J = D(Cgit - Cblood) / h
J = flux
D - diffusion coefficient
h - membrane thickness

Question 11

Facilitated diffusion

Answer 11

Carrier molecules
no energy required
Gradient required

Question 12

Active transport

Answer 12

Carrier molecules requiring energy

Against gradient

Question 13

Endocytosis

Answer 13

Large molecules

Enveloped in vesicle

Question 14

Absorption mechanisms

Answer 14

Passive diffusion
Facilitated diffusion
ACtive transport
Endocytosis

Question 15

Partition coefficient - P

Answer 15

P = [APIoct}
     [APIwater] 
logP = Log [APIoct}             logP = 3 is ideal
                    [APIwater]
            \+ve - hydrophobic
            -ve - Hydrophobic

Question 16

Acid dissociation - Ka

Answer 16

Ka = [A][H] pKa = -logKa
[HA]
High Ka=low pKa=more dissociation=more acidic
Each ionisable group has own pKa

Question 17

Henderson Hasselbach

Answer 17

pH=pKa + log A-
HA
Extent of dissociation at pH values
Larger A-:HA ratio = more dissociation

Question 18

pH partition hypothesis

Answer 18

unionised cross membranes - charge causes lipid solubility loss
low pH = Many h+ = can’t dissociate
high pH = few h+ = easily dissociate

pH = pKa - 50% ionised

Question 19

Lipinski rule of 5 - Good absorption criteria

Answer 19

Fewer than 5 Hbond donors
Fewer than 10 Hbond acceptors
MWT of less than 500
LogP less than 5