1: Clinical Pharmacokinetics 2

Question 1

what are the three components of renal clearance?

Answer 1

CLrenal = filtration + secretion - reabsorption

Question 2

what is a normal GFR?

Answer 2

120 mL/min

Question 3

what types of drugs are filtered by the glomerulus?

Answer 3

only unbound drugs

Question 4

what are two markers for GFR?

Answer 4

creatinine and inulin

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

Question 5

renal clearance and dosage adjustment + corrected dose equation

Answer 5

renal disease often changes drug clearance -> this can be used to adjust dose to maintain the Css

corrected dose= avg dose (pt CLcreatinine/ 100 ml/min)

Question 6

when do you adjust dosages?

Answer 6

only when drug is >50% cleared by renal elimination and renal fxn is reduced to 50% or less of normal

Question 7

first order elimination

Answer 7

• constant % of drug eliminated/time
• when drug dose increases, Css increases proportionately
• how 95% of drugs work
• accumulation + elimination change exponentially for a single dose over time
• linear Cp accumulation with increase in dose

Question 8

zero order elimination

Answer 8

• constant amount of drug eliminated/time
• ER same regardless of [C]
• linear decrease in [C] over time
• non-linear Cp accumulation with increase in dose

Question 9

Michaelis-Menton kinetics: rate of elimination

Answer 9

= (Vmax x C)/(Km + C)

Question 10

definition of Km

Answer 10

[drug] at 50% of Vmax

-measure of the affinity of the substrate for the enzyme

Question 11

definition of half life

Answer 11

time it takes to eliminate 50% of the drug from the body - only applies to first order drugs

Question 12

what is the elimination rate constant?

Answer 12

K or Ke - fraction of Vd elimination remains constant per unit time

Question 13

equation for half life

Answer 13

= 0.693/ Ke = (0.693 x Vd)/ CL

Question 14

is half life dependent on concentration?

Answer 14

newp

Question 15

describe the accumulation and elimination of a drug according to half-lives

Answer 15

95% of final accumulation plateau reached after 4.5x

95% of total dose eliminated after 4.5x

Question 16

why is half life important? (3 reasons)

Answer 16

1. determine time to reach Css
2. determine duration of action
3. determine proper dosing frequency to avoid large fluctuations in Cp

Question 17

how will doubling the dose administered change the duration of action?

Answer 17

increases duration by one half life

Question 18

one compartment model: Vd with elimination

• equation for Vd
• assumptions

Answer 18

Vd = dose/Co

Assumptions:

• FIRST ORDER
• body is ONE homogeneous compartment
• instantaneous mixing

Question 19

two compartments: Vd distribution without elimination

Answer 19

• distribution b/w compartments slower than distribution within each compartment
• distribution phase typically

Question 20

two compartments: Vd distribution with elimination

Answer 20

-distribution to 2nd compartment slower than distribution w/i 1st compartment

Question 21

two compartment model assumptions

Answer 21

• FIRST ORDER
• instant mix in ‘each’ compartment
• slower mix ‘between’ compartments

Question 22

designing dose regimens for i.v. vs p.o: DR

Answer 22

iv: DR = (CL)(Css)
po: DR = (CL x Css)/F

Question 23

designing dose regimens for i.v. vs p.o: loading dose

Answer 23

iv: loading dose = (Vd)(target Cp)
po: loading dose = (Vd x target Cp)/F

Question 24

designing dose regimens: therapeutic window at different values of half life

Answer 24

• if dosing interval = t1/2, Cmax/Ctrough = 2

- if dosing interval t1/2, Cmax/Ctrough > 2 (may exceed therapeutic window)

Question 25

equation to adjust dosage regimen

Answer 25

new rate = (old rate)(desired Css/ measured Css)

Question 26

what is the purpose of therapeutic drug monitoring?

Answer 26

use Cp to:

• individualize dose
• predict effect
• diagnose toxicoses

Question 27

what kinds of drugs are monitored?

Answer 27

• marked PK variability
• narrow therapeutic window
• therapeutic and AE related to [drug]
• desired therapeutic effect difficult to monitor
• inter-individual variation in PK parameters