Pharmacokinetics

Question 1

What is pharmacokinetics?

Answer 1

The study of the kinetics of drug absorption and disposition

Question 2

What is the equation for the concept of distribution (V_D) of drugs?

Answer 2

Volume of beaker = Amount added/[Drug]

V_D = A/[D]_P

Where A = amount of drug in body and [D]_P = concentration of plasma in blood

Question 3

If you want to locate a specific drug in the plamsa what value would you use?

Answer 3

[D]P(target)

A_(target) = V_D x [D]_P(target)

Where A_target it the amount of drug in the body required to achieve [D]_P(target)

Question 4

What is the equation for loading dose?

Answer 4

LD x B = A_target

LD = A_target/B

LD = (V_Dx [D]_P(target))/B

Where B is bioavailability (the fraction od administered dose absorbed from the body)

Question 5

What is the equation best used for loading dose?

Answer 5

LD = (V_D x [D]_P(target))/B

Question 6

What determines the rapid target concentration of a drug in the plasma?

Answer 6

Concentration of drug in plasma, bioavailability and the volume

Question 7

Which will be better distributed to the body and large V_D or a small V_D?

Answer 7

Large

Question 8

As V_D goes up, what happens to the [D]_P in tissue binding?

Answer 8

Goes down

Question 9

How is V_D obtained from the body?

Answer 9

Give bolus of drug, measure plasma levels over time, extrapolate to find plasma level at time 0

VD = amount in body at time 0/[D]_P⁰ = Dose_IV/[D]_P⁰

Question 10

What is the differncce between 1 compartment and 2 compartment V_D?

Answer 10

V_D(final) reached in minutes with 1

VD_(final) reached only after delay with 2

Question 11

What equation would you used if the drug exhibited 1-compartment behavior?

Answer 11

LD = (VD x [D]_P(target))/B

Question 12

What equation would you use for a drug that inhibits 2-compartment behavior?

Answer 12

LD = (V_? x [D]_P(target))/B

? = V_D(aplha) or V_D(beta) depending on trade offs

Question 13

Solve for parameters of Digoxin LD. Given:

[D]_P(target) = 1.5 ug/L

V_D= 580 L

Oral bioavailability = 0.7

Answer 13

Oral LD = (580 L x 1.5 ug/L) /0.7

Oral LD = 1243 ug or 1.2 mg

Question 14

What is the equation for drug clearance?

Answer 14

Cl = Rate of Drug elimination /[D]_P

Question 15

What are the units for Drug Clearance?

Answer 15

Volume/Time

Question 16

Solve for drug clearnace. Given:

Rate of drug elimination = 10 mg/hr

[D]_P = 4 mg/L

Answer 16

Cl = 10 mg/hr / 4 mg/L

Cl = 2.5 L/hr

Question 17

How are most drug eliminated by the body?

Answer 17

First order kinetics

Question 18

Drug clearnance is a determinant of [D]_P at….

Answer 18

Steady state [D]_P^SS

Question 19

When is the steady state said to exist?

Answer 19

Rate of Drug Administration (R₀) = Rate of drug elimination

Input = Output

Question 20

What is the equation for steady state?

Answer 20

[D]_P^SS = Rate of drug eliminiation stead state/ Cl

R₀ = Rate of Drug administration steady state

Question 21

What is the maintance dose (MD)?

Answer 21

AMount of drug taken at regular intervals

Question 22

What is the dosing interval (DI)?

Answer 22

Time between MDs

Question 23

What is bioavailability?

Answer 23

Fraction of administered dose that is absorbed into systemic circulation

Question 24

What is the equation for rate of drug administration?

Answer 24

R₀ = (B x MD) / DI

Question 25

What is the equation for drug clearance steady state?

Answer 25

[D]_P^SS = (B x MD) / (DI x Cl)

Question 26

What is [D]_P^SS dependent on?

Answer 26

The ratios of MD and DI

Question 27

What is [D]_P^SS a major determinant of?

Answer 27

Therapeutic response Toxicity

Question 28

When the goal is to provide [D]_P(target) how is the equation for drug clearance stead state rearranged?

Answer 28

MD/DI = ([D]_P(target) x Cl) / B

Question 29

The rate of elimination most occurs in the ____ and \_\_\_.

Answer 29

Liver and kidney

Question 30

What are the rate of renal elimination and the rate of hepatic elimination?

Answer 30

Cl_R and Cl_H

Question 31

What is the equation for drug clearnance determination of full clearance? (For liver and renal stuff)

Answer 31

Cl = Cl_R + Cl_H

Question 32

What is the rate of renal elimination due to?

Answer 32

Glomerular filtration of drug not bound to plasma proteins Secretion into renal tubulesof acidic and basic drugs by transport systems in proximal tubule

Question 33

What is the rate of renal elimination reduced by?

Answer 33

Reabsoprtion of lipophilic drugs from renal tubule Renal diseases that dec glomerular filtration and tubular secretion of drug Competition between drugs for secretion by transport systems in the proximal tubule

Question 34

What is hepatic elimination due to?

Answer 34

Metabolism of drugs by liver enzymes Secretion of drugs into bile by transport systems in the hepatocytes

Question 35

What is hepatic elimination reduced by?

Answer 35

Ionization of drugs which limits penetration of drug into hepatocytes Competition between drigs for metabolism and/ or transport into bile Liver disease Genetic variation in drug metabolizing enzyme

Question 36

What is heptic elimination increased by?

Answer 36

Induction of liver enzymes by same drug, other drug and/or environmental chemicals Genetic variation in drug metabolizing enzymes

Question 37

What equation tells the rate of drug administration?

Answer 37

MD/DI = ([D]_P(target) x Cl) / B

Question 38

What is the equation for the therapeuric window?

Answer 38

TW = highest [D]_P that is safe/ lowest [D]_P that is therapeutically effective

Question 39

What is the maximum dosing interval (DI_max)?

Answer 39

The longest dosing interval that still provides non-toxic peak plasma levels of drug while providing therapeutically effective trough plasma levels of the drug

Question 40

What is elimination t_1/2?

Answer 40

Time required for drug elimination process to decrease by the amount of drug in the body by 50%

Question 41

What is the equation for maximum dosing interval?

Answer 41

DI_max = 1.44 x t_1/2 x ln (TW)

Question 42

Solve for the oral MD/DI for digoxin. Given: [D]_P(target) = 1.5 ug/L Cl = 6.6 L/hr Oral bioavailability = 0.7

Answer 42

Oral MD/DI = ([D]_P(target) x Cl) / B =(1.5 ug/L x 6.6 L/hr) **/** 0.7 = 14.1 ug/L

Question 43

Calculate DI_max for Digoxin: Given: D_P(effect) \> 0.8 ug/L D_P(toxic) \> 2.5 ug/L t_1/2 = 39 hrs

Answer 43

DI_max = 1.44 x t_1/2 ln (TW) = 1.44 x 39 hrs x ln (2.5/0.8) = 64 hrs

Question 44

Calculate the convenience use for DI of 24 hours (\<64) Oral MD/DI = 14.1 ug/L

Answer 44

Oral MD/24 hrs = 14.1 ug/L Oral MD = 14.1 ug/L x 24 hrs = 338.4 ug =.34 mg

Question 45

What is the equation for half life?

Answer 45

t_1/2 = (0.693 x V_D) / Cl

Question 46

If there is 2 compartment behavior for half life, what value should be used for distribution volume?

Answer 46

V_D(beta)

Question 47

What is time to steady state (t_ss)?

Answer 47

Time required to reach [D]_P^SS if the dosing regimen only involves the repeated adminstration of drug using a specific MD/DI ratio

Question 48

If you have one compartment behavior, four elimination half lives:

Answer 48

Provide 94% of [D]_P^SS when treatment is started Reduce [D]_P to 6% of [D]_P^SS when treatment stopped

Question 49

If 2-compartment behavior, four elimination half-lives:

Answer 49

Provide \> or = 94% of [D]_P^SS when treatment is started Reduce [D]_P to \< or = 6% of [D]_P^SS when treatment stopped

Question 50

What is the equaiton for t_SS for 1 and 2 compartment behaviors?

Answer 50

t_SS = 4 x t_1/2

Question 51

Calculate the t_SS for Digoxin. Given: t_1/2 = 39 hrs

Answer 51

t_SS = 4 x t_1/2 = 4 x 39 = 156 hrs (loading doses often prescribed)

Question 52

What are the steps to designing a dose regimen?

Answer 52

1. Decide whether LD is required (if so calculate) 2. Determine MD/DI ratio 3. Determine DI

Question 53

If a patient has renal disease how would you adjust the drug?

Answer 53

If eliminated by the liver don't worry about it * Re-evaluate need for drug; discontinue if possible * Reduce dose * Inc dose interval * Switch to drug eliminated by liver

Question 54

If a pt has liver disease how would you adjust the drug?

Answer 54

If eliminated by the kidneys don't worry about it * Re-evaluate need for drug; discontinue if possible * Reduce dose * Inc dose interval * Switch to drug eliminated by kidney