E1 L9: Bioavailability and Clearance 4:

Question 1

When fe is 0

Answer 1

Hepatic clearance is the same as renal clearance

Question 2

What directional changes in AUCiv and CL are expected

Answer 2

Decrease clearance, and increased AUCiv

Question 3

What directional changes in AUCpo and F are expected?
Decrease intrinsic decreased oral

Answer 3

Increased oral AUC

Question 4

Q: Assuming 100% oral absorption, co-administration of an enzyme inducer with a low EH drug (Drug X) would:
A. Significantly increase F of drug X
B. Significantly decrease F of drug X
C. Significantly increase CLH of drug X
D. Significantly decrease CLH of drug X

Answer 4

C. Significantly increase CLH of drug X

Question 5

Q: Assuming 100% oral absorption, co-administration of an enzyme inducer with a high EH drug (Drug Y) would:
A. Significantly increase F of drug Y
B. Significantly decrease F of Drug Y C. Significantly increase CLH of Drug Y
D. Significantly decrease CLH of Drug Y

Answer 5

B -significantly in decrease F of drug Y

Question 6

Q: Assuming 100% oral absorption and fe = 0, co-administration of an enzyme inducer with a high EH drug (Drug Y) would:
A. Significantly increase Cl of Drug Y
B. Significantly increase CLpo of Drug Y
C. Significantly increase F of Drug Y
D. Significantly increase AUCiv of Drug Y

Answer 6

B. Significantly increase CLpo of Drug Y

Question 7

Some drugs are eliminated unchanged in the urine. We can determine how much of a drug is excreted unchanged into the urine by collecting and analyzing urine concentration data

Answer 7

Renal excretion

Question 8

Approx. - of cardiac output goes to the kidneys; of the volume - is filtered in the glomerulus; this is the Glomerular filtration rate (GFR) (120ml/min)

Answer 8

20%; 10%

Question 9

Only (bound/unbound) drug is filtered

Answer 9

Unbound

Question 10

Over 90% of the filtered volume is reabsorbed in the

Answer 10

Renal tubules

Question 11

Filtration occurs in the

Answer 11

Glomerulus

Question 12

Filtration depends on

Answer 12

Molecular weight
and unbound drug concentration in plasma (fu)

Question 13

Filtration equation

Answer 13

CLR = Fu * GFR

Question 14

Secretion equation

Answer 14

CLR > fu * GFR

Question 15

Reabsorption equation

Answer 15

CLR < fu * GFR

Question 16

Drug A PK parameters are as follows:
CL: 500 ml/min
fu: 0.95
fe: 1
Q: T/F:
1. Hepatic metabolism is a major elimination pathway
2. T/F; Significant reabsorption occurs

Answer 16

False - Hepatic is not major, it is minor (Fe = 1)
False - when you compare clearance (fe is 1, means clearance is the same as renal clearance)

Question 17

Occurs in proximal tubule

Answer 17

Secretion

Question 18

T/F: secretion is an active carrier mediated process

Answer 18

True
Saturable; there are separate transporters for acids and bases from plasma into urine. In general, neutral drugs are not secreted

Question 19

If rate of excretion > rate of filtration, then infer that

Answer 19

secretion has occurred.

Question 20

Are good substrates for renal transporters and dissociate rapidly from plasma proteins so as not to limit secretion. Amount of secretion is dependent only on renal blood flow e.g. para-amino hippuric acid (ER ~1)

Answer 20

High renal excretion drugs (High ER)

Question 21

Are poor substrates for renal transporters; even through blood sits at the proximal tubule for ~30 seconds, transportation is the limiting step. Amount of secretion depends on unbound concentration of drug in blood and is independent of renal blood flow

Answer 21

Low renal excretion drugs (low ER)

Question 22

Secretion may depend on:

Answer 22

Plasma protein binding (fu)
Kidney blood flow

Question 23

Drugs actively secreted by the kidney: Acids

Answer 23

Penicillin’s
Probenecid
-Share same transporters cam compete with each other situation

Question 24

T/F: Passive process for exogenous products including drugs

Answer 24

True

Question 25

If rate of excretion < rate of filtration

Answer 25

Infer that reabsorption has occurred

Question 26

If CLR < fu * GFR, then

Answer 26

reabsorption has occurred (secretion may have occurred, but reabsorption is greater)

Question 27

Factors affecting renal reabsorption of drugs: properties of drugs and physiological factors:

Answer 27

Properties: Polarity Ionization Physiological factors: Urine flow Urine pH

Question 28

Polar compounds (are/are not) best absorbed

Answer 28

Are not

Question 29

Ionized compounds (are/are not) best absorbed

Answer 29

Are not

Question 30

High plasma protein binding (increases/decreases) drug excretion

Answer 30

Decreases

Question 31

Faster urine flow (increases/decreases) drug excretion

Answer 31

Increases

Question 32

Urine pH can vary widely from

Answer 32

4.5 to 7.5 (average 6.3)

Question 33

Variations of Urine pH are due to forced

Answer 33

acidification/alkalization Respiratory or metabolic acidosis/alaklosis and drugs

Question 34

Urine pH is mostly important for

Answer 34

nonpolar drugs that are weak acids (salicylates) or weak bases (amphetamine)

Question 35

Acidification of urine (decreased pH) promotes reabsorption of

Answer 35

weak acids and promotes CLR of weak bases

Question 36

Alkalization of urine (increased pH) promotes reabsorption of

Answer 36

Weak bases and promotes CLR of weak acid

Question 37

(Phenobarbital is a **weak acid** its renal elim is governed by reabsorption) Q: 1. T/F: Pheno is more ionized in basic urine pH 2. Pheno's renal absorption is less in basic urine pH 3. Pheno's CLR would decrease upon urine alkanization

Answer 37

1. True 2. True - more drug ionized, less reabsorption 3. False

Question 38

Q: For a patient with a phenobarbital I(aspirin) overdose, what drug can increase CLr most significantly

Answer 38

Acetazolamide (alkalize)

Question 39

T/F: Methamphetamine is more ionized in acidic urine vs basic

Answer 39

True

Question 40

T/F: Methamphetamines renal absorption is more acidic in urine pH

Answer 40

False

Question 41

T/F: Methamphetamine's CLR would increase upon acidification

Answer 41

True

Question 42

Drug that is polar in its unionized form is not reabsorbed Strong acids (pKa<3) and strong bases (PKa>12) are completely ionized over urine pH range, therefore undergo little reabsorption Very weak acids (pka > 8) and very weak bases (pKa<6) will be unionized in the urinary pH range and will be reabsorbed in this range, resulting in low CLR and insensitive to pH, e.g. phenytoin (acid) propoxyphone (base)

Answer 42

Situations insensitive to urinary pH (Effects of urine pH on CLR)

Question 43

GFR is influenced by

Answer 43

Filtration

Question 43

Urine flow rate is influenced by

Answer 43

Reabsorption

Question 44

Urine pH is influenced by

Answer 44

Reabsorption

Question 45

Renal transporters are influenced by

Answer 45

Secretion