Ch. 15 Biopharmaceutics and Pharmacokinetics

Question 1

Define absorption:

Answer 1

mechanisms of drug input into the body and into a tissue or an organ within the body

Question 2

Define distribution:

Answer 2

• distribution of a drug into the body’s tissues after it enters systemic circulation
• depends on blood perfusion, cell membrane permeability, and tissue binding

Question 3

Define excretion:

Answer 3

• process by which a drug or its metabolites are removed from the body without further chemical modification
• primary routes include renal excretion, biliary excretion (bile), fecal excretion (intestine)

Question 4

Define disposition:

Answer 4

Disposition can be broken down into distribution and elimination.

Question 5

Define elimination:

Answer 5

• sum of the processes related to drug loss from the body (metabolism and excretion)

Question 6

Define bioavailability:

Answer 6

• bioavailability describes the rate and extent to which the active drug ingredient is absorbed from a drug product and becomes available at the site of drug action

Question 7

Define absolute bioavailability:

Answer 7

• absolute bioavailability (F) is the fraction of an administered dose that reaches the systemic circulation and ranges from F=0 (no drug reaching systemic circulation) to F=1 (complete drug absorption)
• F is determined by comparing the respective AUC values of a test produce to those obtained when the drug is administered intravenously

Question 8

Define relative bioavailability:

Answer 8

• relative bioavailability refers to the availability of a drug product as compared to another dosage form or product of the same drug given in the same dose
• these measurements determine the effects of formulation differences on drug absorption
• obtained by comparing their respective AUC values

Question 9

Point out rates of absorption, disposition, metabolism, and elimination on a curve of plasma level versus time.

Answer 9

Question 10

Define apparent volume of distribution:

Answer 10

• the volume of fluid into which a drug appears to be distributed or diluted

provides a reference for the plasma concentration expected for a given dose and for the dose required to produce a given concentration

Question 11

What are the causes of low bioavailability?

Answer 11

• extensive first-pass metabolism
• intestinal secretion of drugs by MRP2 and P-gp (transporters)
• enterohepatic recirculation
• poorly water-soluble, slowly absorbed drugs
• insufficient time in GI tract

Question 12

What is the biopharmaceutics classification system (BCS)?

Answer 12

• scientific framework for classifying drug substances based on their intestinal permeability and aqueous solubility

Question 13

What are two major transporter superfamilies?

What are examples of members in those families?

Answer 13

• ATP-binding cassette (ABC) (P-gp, MDR1)
• solute carrier family (SLC) (OATP)

Question 14

How do ABS transporters work?

Answer 14

• ABC transporters directly use ATP hydrolysis as the driving force to pump substrates out of cells or prevent them from entereing cells

Question 15

Explain Overton’s rule:

Answer 15

• The entry of any molecule into a cell is the result of its selective solubility in the cell’s boundary
• The more soluble in lipids a molecule it, the greater is permeability

Question 16

What is concerted drug transport?

Answer 16

• occurs when transport of a compound is facilitated across both membrane domains of a polarized cell by membrane transporters
• implies that the transporters on the two domains move drugs in the same direction

Question 17

What is phase I drug metabolism?

Answer 17

• formation of a new or modified functional group or a cleavage
• oxidation, reduction, hydrolysis

these are nonsynthetic reactions

Question 18

What is phase II drug metabolism?

Answer 18

• involve conjugation with an endogenous compound
• typically UDP glucuronic acid, sulfate, acetate, or amino acid

synthetic reactions

Question 19

What is phase III drug metabolism?

Answer 19

• involves transporting the drug, metabolite, or conjugated metabolite across a biologic membrane and out of the body
• membrane transporters

Question 20

What are clinically significant examples of induction and inhibition?

Answer 20

• induction - triazolam becomes ineffective after long-term rifampin treatment because triazolam metabolism in increased
• inhibition - grapefruit juice inhibits CYP3A which then prevents verapamil metabolism , thus increasing the verapamil plasma concentrations

Question 21

How does absorptive capacity differ between the stomach and intestine?

Answer 21

The intestine has a much larger absorptive capacity.