E1 L6: Bioavailability and Clearance 1 Flashcards
Fraction of the administered dose that reaches systemic circulation (the heart)
Bioavailability
The value of F is termed
Relative bioavailability
Bioavailability units and range
No units
Varies between 0-1
Reflects the total amount of drug the body is exposed to
The larger, the more drug the body is exposed to
AUC
F usually indicates bioavailability of
Oral dosage form
The fraction of oral dose that reaches systemic circulation
F (AUCpo/Dosepo)/(AUCIV/DoseIV)
Fraction of drug absorbed
Fa
Fraction of drug that has survived gut metabolism
Fg
Fraction of drug that has survived hepatic metabolsim
Fh
Estimation of F requires
Both oral and IV data
Determinants of F
Intestinal absorption
Intestinal metabolism (insignificant for most drugs)
Hepatic metabolism
Low bioavailability is due to
Poor intestinal absorption and or high hepatic metabolism during the first pass through the liver
How much of drug is gone when it goes through liver
90%
Q: T/F: Drugs that are poorly absorbed from the intestine are expected to show low F values
True - show low bioavailability
Q: T/F: Drugs that experience significant first pass effect are expected to have low F values
True
The proportionality constant relating the rate of drug elimination and the plasma concentration
Clearance
Elimination =
Hepatic clearance + Renal Clearance
Urinary excretion accounts for - of total drug elimation
20%
Systemic blood clearance, total blood clearance, blood clearance
CLb
If all drug molecules are distributed in the plasma
Drug amount in plasma = drug amount in blood
If a drug does not bind to blood cells, blood/plasma concentration ratio is
0.50.6
Certain drugs such as - and - distribute into RBC significantly, having a blood/plasma conc. ratio greater than 15
Tacrolimus and cyclosporine
Q: T/F: When a drug is distributed mainly in the plasma, Vd estimated from blood concentration is larger than that from plasma concentration
True - IV bolus kinetic, distribution is drug specific; in most cases we measure conc in plasma; most measurements based on plasma samples
The proportionality constant relating the rate of drug elimination and drug concentration in plasma
CL
The proportionality constant relating the rate of drug elimination and the drug concentration in blood
CLb
T/F: CLb can be estimated from CL and blood/plasma drug concentration ratio (Cb/Cp)
True
For drugs mainly distributed into plasma Cb/Cp =0.5; That means
CLb = 2*CL
If a drug is mainly distributed in plasma AUCblood =
1/2 of AUCplasma
T/F: After oral admin of 1g drug, you obtain plasma drug concentration vs time. You can estimate AUC from the curve. Using the data, you can calculate CL
False- clearance tells about the rate of drug elimination
T/F: CL is a PK parameter reflecting the rate of drug elimination
True
T/F: CL is smaller for drugs that are eliminated faster
False - larger
T/F: After IV, faster drug elimination leads to smaller AUC and larger CL values
True
T/F: After po, AUC reflects “absorption” as well as elimination
True
