Elimination and Clearance

Question 1

What is drug elimination?

Answer 1

Irreversible removal of drug from the body by all routes of elimination.

Question 2

What is excretion?

Answer 2

Removal of intact drug.

Question 3

What is biotransformation or drug metabolism?

Answer 3

Drug is chemically converted in the body to a metabolite.

Question 4

What are the two major drug elimination organs in the body?

Answer 4

Kidney and liver

Question 5

How are drugs excreted?

Answer 5

Bile, Urine, Sweat, Breast Milk, Exhaled Air

Question 6

What is clearance?

Answer 6

Process of drug elimination from the body or from a single organ without identifying the individual processes involved.
Volume of fluid cleared of drug from the body per unit time.
The proportionality factor that relates rate of drug elimination to the plasma drug concentration.
The loss of drug across an organ of elimination.

Question 7

What is the clearance equation?

Answer 7

Rate of elimination = Cl x Cp

Cp is plasma concentration

Question 8

Will clearance change?

Answer 8

no

Question 9

Will rate of elimination change?

Answer 9

yes

Question 10

What is the equation for fraction of drug excreted?

Answer 10

fe = (Du/FD0) = (ke/k)
fe is fraction excreted
Du is amount of drug cumulative in the urine
F is bioavailability(assumed to be 1 in IV)
D0 is initial dose
ke is rate constant for excretion
k is rate constant efor elimination

Question 11

What is the equation for renal clearance?

Answer 11

ClR = (Du/FD0)ClT = (ke/k)ClT = feClT

Question 12

What is the equation for total body clearance?

Answer 12

ClT = ClR + ClH

Question 13

Total clearance can be determined from what?

Answer 13

total exposure (AUC, area under the curve) following an IV dose.
ClT = (D0/AUC)

Question 14

Renal clearance can be determined how?

Answer 14

From the fraction excreted unchanged and total clearance.

ClR = fe x ClT

Question 15

How is hepatic clearance measured?

Answer 15

Rate and extent of metabolism can rarely be measured directly, but by taking advantage of the additivity of clearance, hepatic clearance is readily estimated as the difference between total and renal clearance.
ClH = (1 - fe) x Cl
ClR = ClT - (feClT)

Question 16

Appearance of drug in the urine is the net result of?

Answer 16

filtration, secretion, and reabsorption.

Question 17

What are the three mechanisms of renal excretion?

Answer 17

Glomerular filtration- passive diffusion of drug across the glomerulus
Tubular secretion -active secretion of some drugs from the blood into the urine.
Tubular reabsorption - reabsorption of some drugs form the urine back into the blood.

Question 18

What is the max glomerular filtration that can occur?

Answer 18

130 mL/min

Question 19

What is creatinine?

Answer 19

Creatinine is an endogenously produced compound that is neither bound to plasma proteins nor secreted and the entire filtered load is excreted into the urine. The renal clearance of creatinine is a estimation of GFR. It is the most common measure of renal clearance.

Question 20

Where does creatinine clearance come from?

Answer 20

muscle breakdown.

Question 21

Creatinine clearance can be calculated by what?

Answer 21

The Cockcroft-Gault equation with 120-130 mL/min being considered normal.
CrCl = (140-age)(IBW) / (72 x SCr) ( x 0.85 if female)
assuming woman have 15 % less muscle
age in years, IBW in kg
male IBW = 50 +2.3(inches over 5 ft)
female IBW = 45.5 + 2.3(inches over 5 ft)
SCr = serum creatinine in mg/dL

Question 22

What is active secretion?

Answer 22

Secretion is inferred when rate of excretion exceeds the rate of filtration. Secretion is apparent when renal clearance is greater than the GFR.

Question 23

What is tubular reabsorption?

Answer 23

Reabsorption occurs if the renal clearance is less than the calculated clearance by filtration.

Question 24

What are the two major components of drug elimination from the body?

Answer 24

Excretion and biotransformation.

Question 25

What is clearance?

Answer 25

The volume of fluid cleared of drug from the body per unit time. It is a constant for first-order processes.

Question 26

The extent of drug reabsorption of weak acids and weak bases is influenced by what?

Answer 26

The pH of the urine and the degree of ionization of the drug.