1: Clinical Pharmacokinetics

Question 1

equation for concentration

Answer 1

[C] = M/V

Question 2

pharmacokinetics (PK) vs. pharmacodynamics (PD)

Answer 2

PK: what the body does to the drug

• how the [drug] changes as it moves through different compartments of your body
• drug disposition: ADME

PD: what the drug does to the body

• describe the relationship b/w the [unbound drug] at the receptor and drug response
• potency, drug effect

PK predicts PD

Question 3

fundamental hypothesis simple statement

Answer 3

predictable relationship b/w plasma (or serum) concentration of drug and its effect

Question 4

3 general goals of PK

Answer 4

• establishing/adjusting dosage regimens
• diagnosis of toxicoses
• withdrawal times for food safety in babies

Question 5

AUC

Answer 5

area under the curve - describes the ‘behavior’ (exposure) of the drug moving through the body

Question 6

bioavailability, F

Answer 6

% of drug entering into circulation
= (% absorbed)(1-Eh)
=AUC (p.o.)/ AUC (i.v.)

Question 7

Eh (hepatic extraction ratio)

Answer 7

fraction of drug extracted by liver in FPM

=(C1-C2)/C1

Question 8

effects of hepatic extraction on bioavailability

Answer 8

low Eh drugs have higher F
-changing enzymatic activity doesn’t significantly change Cp

high Eh drugs have lower F
-changing enzymatic activity does significantly change Cp

Question 9

relative bioequivalence, Fr

Answer 9

= AUC generic/ AUC brand

two considered equivalent if 0.8

Question 10

which form of a drug is active: bound or unbound?

Answer 10

unbound

Question 11

apparent volume of distribution, Vd

Answer 11

-constant relating the amount of drug in the body to the plasma drug concentration
= total drug in body (A)/ plasma [drug] (Cp)

Question 12

why can Vd be much larger or smaller than the physical volume?

Answer 12

uneven distribution in different compartments

Question 13

factors affecting Vd

Answer 13

• MW (drug)
• polarity (drug)
• permeability (drug)
• solubility (drug)
• BINDING (drug and patient)
• blood vol/flow (patient)
• size of organ (patient)
• transporters (patient)
• disease status (patient)

Question 14

steady state concentration, Css

Answer 14

[drug] where rate of drug input = rate of drug elimination

Question 15

maintenance dose rate, DR

Answer 15

rate of drug input to maintain the [drug] at steady state

= (CL)(Css)

Question 16

loading dose vs. maintenance dose

Answer 16

loading dose reached Css faster than maintenance dose

Question 17

loading dose

Answer 17

= (Vd)(target Cp)

Question 18

definition of drug metabolism

Answer 18

IRREVERSIBLE transformation of parent compounds into daughter compounds –> can either terminate action or bioactivate

Question 19

what is the path by which most drugs are excreted?

Answer 19

renal

Question 20

clearance, CL

Answer 20

volume of drug eliminated per unit time
-constant for drug and patient
= dose/ AUC
=

Question 21

elimination rate, ER

Answer 21

mass of drug eliminated per unit time

= (CL)(Cp)

Question 22

elimination rate constant, K or Ke

Answer 22

percent of drug eliminated per unit time

= CL/Vd

Question 23

when DR remains the same, how will changing CL alter Css?

Answer 23

changing CL will proportionately and inversely change the Css

Question 24

organ x clearance, CLx

Answer 24

= organ extraction ratio (Ex) x organ blood flow (Qx)

Question 25

for drugs extensively metabolized by the liver, describe how Eh and Q affect CL

Answer 25

Eh is almost fixed and will barely affect CL, so CL will mainly be determined by Q

-important for drug-drug interactions when hepatic drug metabolism is induced/inhibited and in certain conditions that affect blood flow

Question 26

for drugs with high Eh, how will increased hepatic metabolism affect F and CL?

Answer 26

decreased F

no change in CL

Question 27

for drugs with low Eh, how will increased hepatic metabolism affect F and CL?

Answer 27

no change in F

increased CL