Pharmacokinetics

Question 1

Define pharmacokinetics. (1)

Answer 1

• The study of the fate of drugs from time of administration to time of elimination

Question 2

ADME (4)

Answer 2

• Absorption
• Distribution
• Metabolism
• Elimination

Question 3

Absorption (1)

Answer 3

• how the drug enters the body and systemic circulation

Question 4

Distribution (1)

Answer 4

• how the drug is distributed between circulatory system and tissues

Question 5

Metabolism (1)

Answer 5

• irreversible modification of the drug inside the body

Question 6

Elimination (1)

Answer 6

• how the drug or its metabolites leave the body

Question 7

Define pharmacodynamics (1)

Answer 7

• the branch of pharmacology concerned with the effects of drugs and mechanism of their action

Question 8

What is the aim of pharmacokinetics? (5)

Answer 8

• To assess drug behaviour via mathematical methods
• Requires the use of model systems – compartmental models
• Biological system – interconnecting compartments
• A compartment = a group of tissues with similar blood flow & drug affinity
• Model allows relationship to be expressed as equations

Question 9

Compartment models (6)

Answer 9

• Compartments communicate via reversible processes
• Rate constants are used to measure rate of entry/exit of drug
• Distribution of drug is rapid & homogenous within a compartment
• Each drug molecule has equal chance of leaving
• All models are based on a central compartment = plasma + highly perfused tissues (liver and kidneys)
• Elimination occurs only from the central compartment

Question 10

Define clearance (1)

Answer 10

• volume of blood in a specific region of the body cleared of the drug per unit time

Question 11

Define half-life (1)

Answer 11

• the time it takes for plasma concentration of a drug to drop by half

Question 12

Define rate of elimination (1)

Answer 12

• describes the fraction of drug eliminated per unit of time

Question 13

Define bioavailability (2)

Answer 13

• fraction of drug entering the general circulation
• amount of drug entering general circulation ÷ dose administered

Question 14

Calculate apparent volume of distribution (Vd) (1)

Answer 14

• Vd = Dose (D) ÷ Drug concentration in plasma (Cp)

Question 15

Calculate clearance (CL) (1)

Answer 15

• CL = rate of elimination from entire body (kel) ÷ drug concentration in plasma (Cp)

Question 16

Calculate half-life (T1/2) (1)

Answer 16

• T1/2 = 0.693 (or ln2) ÷ rate of elimination (kel)

Question 17

Calculate rate of elimination (kel) (1)

Answer 17

• kel = 0.693 (or ln2) ÷ half-life (t1/2)

Question 18

IV bolus kinetics (3)

Answer 18

• Inject whole dose at a time/time 0
• Elimination starts immediately
• Elimination is a first order process – for a given time, concentration is halved (i.e., 100%, 50%, 25%, 12.5% etc.)

Question 19

IV Infusion kinetics (4)

Answer 19

• Injection of a drug at a steady state
• Initial increase in plasma concentration due to positive difference between rate of infusion and rate of elimination
• As Cp increases over time, the rate of elimination increases
• Eventually a steady state concentration is reached

Question 20

Oral administration kinetics (4)

Answer 20

• Balance between absorption and elimination
• Cp (t) reaches a maximum drug concentration (Cmax) after a particular time (tmax)
• Elimination starts as soon as drug enters the plasma. Since Cp (t) initially rises due to absorption, rate of elimination increases with increasing Cp (t)
• Once all of the drug is absorbed, elimination becomes dominant

Question 21

How does the calculation of the PK parameters help in rational drug design? (4)

Answer 21

• PK parameters (ADME) provide info on what type of modification to the drug would be needed to improve PK properties
• Inactivation due to metabolism/elimination: ‘stabilise’ the drug, i.e., improve its half-life by modifying relevant chemical group in the drug molecule
• Poor uptake: if it will not pass cell membranes it may be too water soluble; reduce the polarity i.e., redesign drug molecule to be more hydrophobic
• Are its metabolites toxic or safe (or more therapeutically active)