Lecture 32: Clinical Pharmocokinetics 1

Question 1

Goal of pharmacokinetics

Answer 1

• Maximize theraputic response

- Minimize bad reaction/risks

Question 2

3 functions of Plasma Concentration

Answer 2

1) Rate of input of the drug into plasma (blood)
2) Rate of distribution of drug into tissues
3) Rate of elimination of the drug

Question 3

Volume of distribution

Answer 3

• Apparent space in the body available to the drug
• Volume required to get an equal concentration of drug in body and blood

Vd= Amount of drug in the body/Plasma drug concentration

• Higher VD = Extravascular tissue > vascular compartments (
• Lower VD = Completely retained within vascular compartment

-Used to determine loading dose to achieve target plasma [ ]

-Vd= Dose/C0 
(C0= plasma [ ] at the time = 0)

Question 4

If a drug is bound to peripheral tissues or partitioned into body fat how will it affect VD?

Answer 4

• [ ] in plasma = low

- Vd could be very high

Question 5

VD graph

Answer 5

• Y= Plasma drug [ ]
• X= Time

Rapid falls = distribution phase

Slower phase = elimination phase

(Log = straight line)

Question 6

How do you calculate dose?

Answer 6

Dose = Vd X TC

TC = target plasma concentration

Question 7

Clearance

Answer 7

-Volume of blood cleared of drug over time

CL= Rate of elimination of drug (Amount/time)/Plasma drug concentration (Amount/volume)

-Kidneys/liver = drug elimination

Question 8

First Order Elimination

Answer 8

• CL (clearance) = constant over plasma [ ]
• Most drugs follow this order
• Rate of elimination = CL X C
• Rate of elimination = Vmax X C/Km + C

-Occurs because drug elimination enzymes/transporters aren’t saturated (Way more enzymes and transporters vs drugs)

Question 9

First order Graph

Answer 9

• Decays exponentially, constant amount of drug is decayed over time
• Rate of elimination is directly proportional to drug [ ]
• Plotting log C against Time = straight line

Question 10

Half-life

Answer 10

• Time taken to reduce 50% of drugs in the body
• Constant for drugs in first order
• Can increase or decrease by 50% from Current (C) and Steady-state concentration (Css) = peak plasma concentration -depends on infusion is occurring

T1/2= 0.693 x VD/ CL

Question 11

What happens after 4 half lives?

Answer 11

1) Drug has been effectively eliminated

OR

2) Steady state is attained

Question 12

Effects on VD:

What increases half life

Answer 12

1) Obesity

2) Pathologic fluid

Question 13

Effects on CL

What happens to half-life?

Answer 13

Ageing = Increased
CYP induction = Decreased
CYP inhibition = Increased
Cardiac failure = Increased
Liver failure = Increased
Renal failure = Increased

Question 14

What drugs exhibit a zero order elimination

Answer 14

1) Aspirin (High doses)
2) Ethanol
3) Phenytoin

“APE”

Question 15

Zero Order Elimination

Answer 15

• Saturated (Just enough enzymes for elimination, not a surplus like first order)
• Constant amount of drug eliminated over time
• The rate of elimination is maximal and independent of drug concentration