L3 Pharmacokinetics II: Drug Elimination and Multiple Dosing

Question 1

Vd (volume of distribution) = ?

Answer 1

Dose/C0 (initial concentration)

Question 2

For all drugs that obey first-order kinetics, it takes ___ half-lives to reach steady state.

Answer 2

4-6

Question 3

Loading dose = ?

Answer 3

[Cp (peak desired) * Vd]/F

Question 4

Why do we use loading doses?

Answer 4

They more rapidly achieve a therapeutic drug level.

Question 5

True or false - the time to reach steady state is reduced by the loading dose.

Answer 5

False - it is not reduced.

Question 6

Maintenance dose = ?

Answer 6

[CL * Cp * T (dosing interval)] / F

Question 7

What is the maintenance dose?

Answer 7

The dosing strategy used to maintain a steady state of drug in the body

Question 8

What is the primary determinant for calculating the maintenance dose?

Answer 8

Clearance

Question 9

What is the target concentration for a maintenance dose?

Answer 9

The middle of the steady-state

Question 10

What is irreversible drug removal from the plasma through an eliminating organ?

Answer 10

Elimination clearance

Question 11

What is intercompartmental clearance?

Answer 11

Drug distribution between plasma and tissues (bidirectional process)

Question 12

Maintenance dosing rate = ?

Answer 12

Rate of elimination = CLe * Cp

Question 13

Css (steady-state concentration) = ?

Answer 13

[Dosing Rate * F]/CL

Question 14

In steady state, the rate of drug administration = ?

Answer 14

Rate of drug elimination

Question 15

True or false - the time to steady-state is independent of dosage.

Answer 15

True

Question 16

Fluctuations in steady-state are proportional to ___.

Answer 16

Dosage interval/half-time

Question 17

What blunts fluctuations in steady-state?

Answer 17

Slow absorption

Question 18

Steady state concentration is proportional to ___.

Answer 18

Dose/dosage interval

Question 19

Steady-state concentration is inversely related to ___.

Answer 19

CL/F

Question 20

When using a continuous infusion, steady state concentration is proportional to ___ and inversely related to ___.

Answer 20

Infusion rate; CL

Question 21

I (infusion rate) = ?

Answer 21

CL * Css

Question 22

CL (when drug administered by continuous infusion) = ?

Answer 22

I / Css

Question 23

Describe the elimination rate of the drug in first-order kinetics.

Answer 23

It is a constant fraction of the drug remaining in the body per unit time.

Question 24

First-order elimination rate = ?

Answer 24

-kC

Question 25

Most drug obey what type of kinetics?

Answer 25

First-order

Question 26

C (first-order) = ?

Answer 26

C0*e^-kt

Question 27

Drugs that are eliminated primarily by ___ may display zero-order kinetics.

Answer 27

Metabolism

Question 28

Describe the elimination rate of the drug in zero-order kinetics.

Answer 28

A fixed amount is metabolized per unit time

Question 29

Zero-order elimination rate = ?

Answer 29

dC/dt = -k

Question 30

What two main drugs display zero-order kinetics?

Answer 30

Phenytoin, ethanol

Question 31

C (zero-order) = ?

Answer 31

C0 - kt

Question 32

Describe the general principle of dose-dependent kinetics.

Answer 32

When a drug's elimination is mediated predominantly by metabolism, its elimination will tend to follow first-order kinetics when C << Km of the metabolic enzymes, but will follow zero-order kinetics when C >> Km of the metabolic enzymes.

Question 33

dC/dt = ? (no adjustments)

Answer 33

-[Vmax * C]/[Km + C]

Question 34

dC/dt = ? (first-order, C << Km)

Answer 34

-[Vmax * C]/Km

Question 35

dC/dt = ? (zero-order, C >> Km)

Answer 35

-Vmax

Question 36

What is the volume of plasma cleared of drug per unit time?

Answer 36

Elimination clearance (units of flow - mL/min)

Question 37

CL total = ?

Answer 37

CL renal + CL hepatic + CL other

Question 38

Elimination half-life = ?

Answer 38

Time to eliminate 50% of the body content of the drug = (0.69Vd)/CL

Question 39

t 0.90 = ?

Answer 39

Time to reach steady state = 3.3(t 1/2)

Question 40

What is the dosing rate equation when renal failure is present?

Answer 40

Normal dosing rate * [CL renal failure/CL normal]

Question 41

How can a dosing rate by reduced in renal insufficiency?

Answer 41

1. Reduce the dose 2. Increase the dosing interval 3. Both

Question 42

What is creatinine clearance rate (CrCL)?

Answer 42

The volume of blood plasma that is cleared of creatinine per unit time; approximates GFR

Question 43

CrCL = ?

Answer 43

[(140-age)(body wt. in kg)]/(72*serum [Cr] in mg/dL) Reduce estimates by 15% in females

Question 44

What are the three determinants of hepatic drug clearance?

Answer 44

1. Hepatic blood flow (rate of drug delivery to eliminating organ) 2. Plasma protein binding (fraction of drug available for clearance) 3. Intrinsic clearance (hepatocellular metabolism/biliary excretion)

Question 45

CL (hepatic) = ?

Answer 45

Q[(f*CL intrinsic)/(Q + [f*CL intrinsic])] ``` Q = liver blood flow f = free fraction (unbound) ```

Question 46

CL (hepatic) when drugs have low hepatic extraction = ?

Answer 46

f * CL intrinsic (Q >> f* CL intrinsic) Examples: warfarin and phenytoin

Question 47

CL (hepatic) when drugs have high hepatic extraction = ?

Answer 47

Q | Q << f* CLint