Bioavailability and Clearance I + II

Question 1

Bioavailability

Answer 1

-fraction of dose that reaches systemic circulation
-NO UNITS
-between 0 and 1

Question 2

Bioavailability calc

Answer 2

F= (AUC/DOSE)/(AUC/DOSE)

Question 3

Relative bioavailability

Answer 3

-tab/sol

Question 4

Absolute bioavailability

Answer 4

-compare to IV

Question 5

AUC

Answer 5

-reflects total amt of drug the body is exposed to
-proportional to dose in linear kinetics

Question 6

F = Fa x Fg x Fh

Answer 6

F = frac absorbed x frac survived gut x frac survived liver

Question 7

Determinants of F

Answer 7

-intestinal absorption
-intestinal metabolism (usually insignificant)
-hepatic metabolism

Question 8

Low bioavailability

Answer 8

-poor absorption or high metabolism

Question 9

first pass effect

Answer 9

-significant loss of drug during first pass through the liver after oral administration

Question 10

First pass metabolism of IV

Answer 10

-25% of the frac of drug metabolized by liver

Question 11

Clearance

Answer 11

-proportionality constant relating rate of drug elimination and plasma concentration

Question 12

most drug molecules are found in

Answer 12

plasma

Question 13

Cb/Cp of Drugs that do not bind to blood cells

Answer 13

0.5-0.6

Question 14

Vd of a drug mainly distributed in plasma will be ____ when estimated from Cb than Cp

Answer 14

LARGER

(Vd=dose/C0)

Question 15

for most drugs that distribute in plasma, CLb is

Answer 15

DOUBLE the CL

Question 16

extraction ratio

Answer 16

-fraction of hepatic plasmas flow the drug is completely cleared
-property of drug

Question 17

Eh high drugs

Answer 17

EH>0.7
-good substrates of enzymes
-protein binding does not limit metabolism

Question 18

low Eh

Answer 18

EH<0.3
-high protein binding
-OR low enzyme activity
-limited hepatic elimination

Question 19

if EH is around 1

Answer 19

CLh approaches QH

Question 20

intrinsic clearance

Answer 20

-ability of liver to metabolize drug independent of binding restrictions (in free form)
-property of drug
-in vitro

Question 21

CLint values

Answer 21

-volume/time
-greater than 0

Question 22

large CL int drugs

Answer 22

-rapidly metabolized by liver when unbound

Question 23

small CLint drugs

Answer 23

take longet to be metabolized by liver in unbound form

Question 24

CLint obtained from

Answer 24

initial experiments
-vmax/km

Question 25

enzyme inducers effect on CLint

Answer 25

-increases

Question 26

enzyme inhibitor effect on CLint

Answer 26

-decrease

Question 27

inc free fraction of low Eh drugs

Answer 27

has significant effects on its Eh

Question 28

increasing free fraction of high Eh drugs

Answer 28

insignificant effects on its Eh

Question 29

Hepatic plasma flow (QH)

Answer 29

-decreased by heart/liver disease states
-dec by B-blocker
-INCR by food

Question 30

Hepatic enzyme activity (CLint)

Answer 30

-DEC by liver disease, dietary deficiency, enzyme inhibitors
-INC by enzyme inducers

Question 31

binding to plasma proteins (fu)

Answer 31

-liver disease dec plasma protein concentration

Question 32

factors affecting CLh

Answer 32

-QH
-CLint
-fu

Question 33

low EH drugs only effected by

Answer 33

-CLint
-fu

Question 34

high EH drugs affected by

Answer 34

QH

Question 35

PK parameter reflecting rate of elimination from the body

Answer 35

CL

Question 36

PK parameter reflecting rate of elimination from the liver

Answer 36

-CLh

Question 37

PK parameter reflecting the rate of drug elimination effected by enzymes

Answer 37

CLint