Week 2C - Clearance

Question 1

clearance

Answer 1

• most important PK parameter/imp for designing drug reigmens
• measures body’s ability to clear drug from body (irreversible elimination)
• rate of elimination = dX/dt = CL x C
• normally a constant for each drug in each individual.
• elimination by metabolism or excretion
• typically CL is additive:
CLTotal = CLRenal +CLHepatic +CLOther

Question 2

clearance units

Answer 2

volume/unit time

ex: L/h, L/day or mL/min
- sometimes, the units are expressed in volume/unit time/kg BW, which must be multiplied by the individual’s body weight

Question 3

• what does it mean if the clearance of a drug by

the liver is 60 L/h?

Answer 3

• the liver blood flow is 90 L/h

* it means that 60/90 = 2/3 of the drug is irreversibly removed as it recirculates through the liver

Question 4

the most desirable outcome for clearance

Answer 4

to maintain a stable ‘steady-state’ drug concentration (Css) within a target therapeutic window

Question 5

‘Maintenance dose’ (M.D.) is

Answer 5

required during a multiple dosage regimen to maintain steady concentrations within therapeutic range. achieved when accumulation of drug in blood is 0.
acc = dX/dt = 0
MD = CL x Css

Question 6

MD units

Answer 6

CL (L/H) x Css (Mg/L)

= mg/h

Question 7

• what is an appropriate maintenance dose of
phenobarbital for an epileptic patient to achieve
a therapeutic concentration of 20 mg/L?
• based on studies of population kinetics, the
phenobarbital CL for an average patient is 6.5
L/day

Answer 7

M.D. = CL x Css
= 6.5 L/day x 20 mg/L
= 130 mg/day