Clinical Pharmacokinetics

Question 1

renal clearance

Answer 1

CLrenal = filtration + secretion - absorption

Question 2

For reabsorbed drugs, renal CL is dependent on

Answer 2

urine flow rate

Question 3

markers for GFR

Answer 3

creatinine and insulin

Question 4

Normal glomerulus filtration rate (GFR)

Answer 4

120 mL/min

Question 5

properties of creatinine and insulin

Answer 5

unbound to plasma proteins
neither secreted nor reabsorbed
about 100mL/min

Question 6

Adjusted/Corrected dose to maintain Css (in renal disease) =

Answer 6

average dose * (Patients’ creatinine clearance/100 mL/min)

Question 7

When is dose adjustment necessary?

Answer 7

when a drug is >50% clearned by renal elimination and renal function is reduced to half of normal or less

Question 8

What do you do if other elimination routes are involved (liver)?

Answer 8

the corrected dose should be the sum of adjusted dose for each elimination route
Corrected dose = adjusted dose for renal + adjusted dose for liver

Question 9

First order elimination

Answer 9

when the drug dose is increased, the Css will increase proportionately

Question 10

DR =

Answer 10

CL * Css

Question 11

At steady state, DR =

Answer 11

ER = CL * Css

Question 12

95% of drugs within their therapeutic range of concentration fall under which type of elimination

Answer 12

first order elimination (accumulation and elimination of the drug change exponentially)

Question 13

5% of drugs at their therapeutic concentration fall under which type of elimination

Answer 13

zero-order elimination (the drug elimination capacity is saturated)

Question 14

ER =

Answer 14

CL * Cp

Question 15

drug elimination rate as a result of zero-order elimination

Answer 15

drug elimination rate is constant regardless of drug concentration (decrease will be in a linear fashion, accumulation of drug concentration will be non-linear)

Question 16

drug examples of zero-order elimination

Answer 16

ethanol (over most of its Cp range)

phenytoin and aspirin (high therapeutic or toxic concentration)

Question 17

First order elimination

Answer 17

the amount of drug eliminated per unit time is proportional to [C]; same % of drug is eliminated per unit time

Question 18

Zero order elimination

Answer 18

a constant amount of drug is eliminated per unit time; same AMOUNT of drug is eliminated per unit time

Question 19

What happens when you increase a dose with a first-order elimination drug?

Answer 19

Cp is linearly accumulated along with the DOSE

Question 20

What happens when you increase a dose with a zero-order elimination drug?

Answer 20

Cp is non-linearly accumulated along with the DOSE (elimination is limited because it is saturated)

Question 21

Rate of elimination =

Answer 21

Vmax * C / Km + C

Michaelis-Menten Kinetics

Question 22

Vmax

Answer 22

the max velocity of a reaction at very high drug concentration

Question 23

Km

Answer 23

the drug concentration at 50% of Vmax; a measure of the affinity of the substrate to the enzyme

Question 24

What assumptions do you need to ask about drugs before you can do calculations?

Answer 24

If this drug first-order or zero-order elimination?

Question 25

Half life (T 1/2)

Answer 25

the time it takes the body to eliminate 50% of the rug from the body

Question 26

The fraction of Vd eliminated (remains constant per unit time)

Answer 26

elimination rate constant (Ke or K)

Question 27

Elimination rate constant (Ke)

Answer 27

the fraction of drug eliminate/time

Question 28

Elimination rate (ER)

Answer 28

the amount of drug eliminated/time

Question 29

Ke =

Answer 29

CL / Vd

Question 30

T 1/2 =

Answer 30

0.693 / Ke = 0.693 * Vd/CL

Question 31

Which two parameters are half life determined by?

Answer 31

Vd and CL

Question 32

Is half-life dependent on the drug concentration?

Answer 32

No, independent of drug concentration

Question 33

slope of the linear semi-log T1/2 plot?

Answer 33

slope is the same at Ke