F and CL part 1

Question 1

Bioavailability

Answer 1

Fraction of the administered dose that reaches system circulation

Can be calculated relative to administration of another dosage form

If the other dosage form is IV, then F is termed the (absolute bioavailability)

If the reference dosage form is another dosage form, the value for F is termed the relative bioavailability

no units

ranges from 0 to 1

Question 2

Oral bioavailability (F)- AUC

Answer 2

AUC reflects the total amount of drug the body is exposed to

Larger AUC means that the body is exposed to a larger amount of drug

AUC is proportional to linear kinetics

Since oral route is the most common, F usually indicates absolute bioavailability of oral dosage form

Question 3

Equation for F

Answer 3

F= Fa x Fg x Fh

Fa= fraction of drug absorbed
Fg= fraction of drug that has survived gut metabolism
Fh= fraction of drug that has survived hepatic metabolism

Estimation of F requires both oral and IV data

Question 4

Determinants of F

Answer 4

Intestinal absorption
Intestinal metabolism
Hepatic metabolism

Low F is due to poor intestinal absorption or high hepatic metabolism

Question 5

First pass effect

Answer 5

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

If you have a drug that is significantly metabolized by the liver during a single pass 90% of drug is metabolized every time the drug goes through the liver

Question 6

Clearance (CL)

Answer 6

clearance is the proportionality constant relating the rate of drug elimination and the plasma concentration

Question 7

ORGAN CL

Answer 7

liver and kidney are major organs of drug elimination

elimination= hepatic metabolism + renal excretion

CL= CLh + CLr

Question 8

Renal excretion

Answer 8

most drugs are eliminated by metabolism to polar metabolites and the metabolites are excreted in the urine. Some drugs are eliminated unchanged in urine

Question 9

Fe

Answer 9

fraction of drug excreted unchanged in the urine

Fe=CLr/CL
CLr= CL x Fe
CLh= CL-CLr

Question 10

Different CL terms

Answer 10

most drug molecules are found in the plasma

certain drugs such as tacrolimus and cyclosporine bind to RBC significantly, typically for these they are measured using blood samples

For most drugs that distribute in plasma, CLb>CL

Question 11

Plasma concentration vs. Blood concentration

Answer 11

most drugs distribute into plasma

if all drugs are in plasma then it will equal drug amount in blood

Cb/Cp=0.5

If a drug does not bind to blood cells of the drug is 0.5-0.6

Question 12

Systemic plasma clearance

Answer 12

the proportionality constant relating the rate of drug elimination and
the drug concentration in plasma

Question 13

Blood clearance

Answer 13

the proportionality constant relating the rate of drug elimination and
the drug concentration in blood

can be estimated from Cb/Cp

Question 14

CL vs. CLb

Answer 14

CL=doseiv/AUCiv

CLb= Doseiv/ AUCblood, iv