Bioavailability Concepts

bioavailability:

fraction of dose that is systematically available

fraction of the dose absorbed (F_a):

amount of drug that is absorbed into the intestinal enterocyte from the GI lumen; NO 1st pass metabolism is considered

What are the two classifications of bioavailability?

• absolute

• relative

absolute bioavailability:

• comparing oral to IV administration of the SAME drug

• calculation: AUC_oral / AUC_IV

• only works for the SAME dose

relative (comparative) bioavailability:

• one drug product compared to another form or product

• calculation (for SAME dose): AUC_A / AUC_B

• calculation (for DIFFERENT dose): (AUC_generic / Dose_generic) / (AUC_brand / Dose_brand)

What types of studies can rate of absorption be assessed?

in vitro studies only; rates cannot be directly measured in vivo

What happens if absorption is increased?

• T_max decreases

• C_max increases

• ka = K at a sooner time and higher concentration

What happens if excretion is increased?

• T_max decreases

• C_max decreases

• ka = K at a sooner time and higher concentration

Bioequivalence:

comparison of bioavailability between different drugs to see if they are bioequivalent or not

Which two parameters must be within -20% to 25% with a 90% confidence interval to be considered bioequivalent?

AUC and C_max

A patient has a renal disease with decreased GFR. The patient will need to take amoxicillin for treating urinary tract infection. The bioavailability of the orally administered capsule in this patient will be altered.

False; clearance doesn’t affect bioavailability so UTI is not relevant

A patient had a heart disease with decreased blood flow rate to the liver. The patient will need to take amoxicillin to treat UTI. Approximately 70% of the drug was recovered intact from the urine in healthy individuals, indicating 1st pass metabolism. The bioavailability of the drug in this patient will be altered.

False; the drug is a LERD and hepatic clearance is not affected